Zhanming Sha; Panpan Zhang
Abstract
Background: The relationship between genetic polymorphism and postoperative pain and the prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy is not fully understood. Objective: To examine whether lncRNA-GAS5 and its promoter region rs145204276 polymorphism can predict ...
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Background: The relationship between genetic polymorphism and postoperative pain and the prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy is not fully understood. Objective: To examine whether lncRNA-GAS5 and its promoter region rs145204276 polymorphism can predict postoperative pain and prognosis of the patients with HCC undergoing hepatectomy. Methods: Seventy patients with HCC undergoing hepatectomy were enrolled. The lncRNA-GAS5 levels in CD4+ T cells from peripheral blood mononuclear cells (PBMC-CD4+ T cells) and tumor tissues were measured by qRT-PCR. Genotyping analysis of rs145204276 was performed using the TaqMan platform. PBMC-CD4+ T cells were isolated and the cytokine levels in helper T (Th) cells were determined by flow cytometry. Patients with Ins/Ins genotype carrying the rs145204276 polymorphism were allocated into the Ins group, and others were allocated into the Del group. Results: The lncRNA-GAS5 level decreased significantly in PBMC-CD4+ T cells and tumor tissues compared with the healthy controls and corresponding adjacent non-tumor tissues. The patients with Del/Del genotype showed significantly higher lncRNA-GAS5 expression in PBMC-CD4+ T cells, lower postoperative pain scores, and better overall survival. LncRNA-GAS5 expression in PBMC-CD4+ T cells was negatively associated with IL-6, IL-17, and the RORγT/CD3 ratio (an indicator of TH17 polarization). Conclusion: LncRNA-GAS5 expression and its promoter region rs145204276 polymorphism are prognostic biomarkers that can predict postoperative pain of patients with HCC undergoing hepatectomy.
Zhi-Hui Wang; Yue Wu; Zi-Wei Dai; Yuan-Yuan Dong; Bin Wang
Abstract
This paper has aimed to review the available evidence on the association between Interleukin (IL) -10 -1082G/A, -592C/A gene polymorphisms and the risk of human immunodeficiency virus-1(HIV-1) infection. The data of PubMed updated in May 2021 were retrieved. The HIV infection risks were estimated in ...
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This paper has aimed to review the available evidence on the association between Interleukin (IL) -10 -1082G/A, -592C/A gene polymorphisms and the risk of human immunodeficiency virus-1(HIV-1) infection. The data of PubMed updated in May 2021 were retrieved. The HIV infection risks were estimated in allelic, recessive, dominant, homozygous, heterozygous, over-dominant models of IL-10-1082G/A and-592C/A gene locus as odds ratio (OR) with the corresponding 95% confidence interval (95% CI). The correlation was not significant between -1082G/A polymorphism and HIV-1 susceptibility (allelic model (G vs. A: OR (95% CI)=0.968 (0.878-1.067)); recessive model (GG vs. AA+AG: OR (95% CI)=0.940, (0.771-1.146)); dominant model (GG+AG vs. AA: OR (95% CI)=0.967(0.846-1.106)); homozygous model (GG vs. AA: OR (95% CI)=0.971(0.780-1.209)); heterozygous model (AG vs. AA: OR (95% CI)=0.988(0.797-1.224)) and over-dominant model (GG+AA vs. AG: OR (95% CI)=0.969(0.781-1.201)). IL-10-592C/A polymorphism might be related to HIV-1 in allelic model, dominant model, homozygous model and heterozygous model (OR (95% CI)(0.796-0.965); OR (95% CI)=0.793(0.664-0.948); OR (95% CI)=0.755,(0.612-0.930); OR (95% CI)=0.820(0.679-0.991), respectively), but not to recessive model and over-dominant model (OR (95% CI)=0.882(0.770-1.010) and OR (95% CI)=1.009(0.897-1.148)).
Mohammad Asgharzadeh; Davoud Sanajou; Hossein Samadi Kafil; Mehdi Farhoudi; Daryoush Savadi Oskouei; Fatemeh Khaki-Khatibi; Fatemeh Ahmadi; Manouchehr Fadaee; Ali Vegari; Vahid Asgharzadeh; Jalil Rashedi; Behroz Mahdavi Poor; Pourya Gholizadeh
Abstract
Background: Changes in the expression of cytokines as the result of the single nucleotide polymorphisms (SNPs), can affect the incidence of multiple sclerosis (MS). Objective: To investigate the relationship between the frequencies of interleukin-10 (IL-10)-1082 A/G (rs1800896) and CCR5-delta32 genotypes ...
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Background: Changes in the expression of cytokines as the result of the single nucleotide polymorphisms (SNPs), can affect the incidence of multiple sclerosis (MS). Objective: To investigate the relationship between the frequencies of interleukin-10 (IL-10)-1082 A/G (rs1800896) and CCR5-delta32 genotypes and susceptibility to MS in the Iranian Azari population. Methods: IL-10-1082 A/G SNP and the CCR5-delta32 were genotyped in 152 patients suffering from MS and 242 healthy non-relatives by allele specific-PCR and simple PCR methods, respectively. Results: The frequencies of AA (37.6%) and AG (55.9%) genotypes of IL-10-1082 were significantly high in the control (p = 0.021) and MS patients (p = 0.015), respectively, with no statistical difference between these groups. There was no significant difference in the CCR5 gene based on the possession of wild/wild and wild/del32 genotypes between MS patients and the control group. The del32/del32 genotype was not seen in any of the investigated groups. Tobacco (cigarettes and hookahs) consumption was higher among the MS patients (p=0.004), and this has the potential to raise the risk of MS in both the individuals and their family. However, it had no significant relation with the frequency of different genotypes of the IL-10-1082 and the CCR5. Conclusion: Our finding conclude on possible role of AA genotype of IL-10 -1082 as a protective factor in MS.
Yousef Khanjari; Morteza Oladnabi; Nafiseh Abdollahi; Ahmad Heidari; Saeed Mohammadi; Alijan Tabarraei
Abstract
Background: Programmed cell death protein 1 (PD-1) is a negative costimulatory molecule with immunomodulatory properties. Recently, PD-1 gene defects have attracted attention in the pathogenesis of SLE. Objective: Here, we assessed the association of PD-1 gene polymorphisms in intron 4 and haplotypes ...
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Background: Programmed cell death protein 1 (PD-1) is a negative costimulatory molecule with immunomodulatory properties. Recently, PD-1 gene defects have attracted attention in the pathogenesis of SLE. Objective: Here, we assessed the association of PD-1 gene polymorphisms in intron 4 and haplotypes with the susceptibility to SLE. Method: Seventy-six SLE patients and 159 healthy controls were included. We screened the polymorphisms by amplifying the intron 4 of the PD-1 gene with the specific primers followed by sequencing. Results: Two distinct SNPs were identified (rs6705653 and rs41386439) within the intron 4 of the PD-1 gene. The AA genotype of +7499 (G/A) SNP was associated with the higher risk of SLE [OR=3.31, 95% CI (1.25-8.76), p-value=0.045], while A allele was identified as a risk allele [OR=1.75, 95% CI (1.10-2.76), p-value=0.015]. However, no significant association was observed between the allele and the genotype frequencies of +7209 (C/T) polymorphic region of the PD-1 gene and susceptibility to SLE. Haplotype analysis showed the significantly higher presence of H2 haplotype (AC; +7499/+7209) [OR=1.70, 95% CI (1.24-2.33), p-value=0.0012] in SLE patients. Conclusion: To the best of our knowledge, this is the first report of the significant association of PD-1 +7499 (G/A) SNP with the SLE susceptibility and the first detection of both polymorphic loci in a population from Iran. However, more investigations are necessary to confirm these findings.
Zahra Mehraji; Ali Farazmand; Alireza Esteghamati; Sina Noshad; Maryam Sadr; Somayeh Amirzargar; Mir Saeed Yekaninejad; Aliakbar Amirzargar
Volume 14, Issue 3 , September 2017, , Pages 223-230
Abstract
Background: Graves’ disease (GD), a highly rampant autoimmune disorder of the thyroid gland, is responsible for 60-80% of the clinical cases of hyperthyroidism. Over the past decades, genetic association studies have identified several GD susceptibility loci in CTLA-4, TSHR and major histocompatibility ...
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Background: Graves’ disease (GD), a highly rampant autoimmune disorder of the thyroid gland, is responsible for 60-80% of the clinical cases of hyperthyroidism. Over the past decades, genetic association studies have identified several GD susceptibility loci in CTLA-4, TSHR and major histocompatibility complex regions. The information on the association between the human leukocyte antigens (HLA) and GD among Iranians is scarce. Objective: To identify HLA polymorphisms that might confer susceptibility or protect against GD. Methods: Eighty unrelated patients with a confirmed diagnosis of GD were included in the case group. The control group consisted of 180 unrelated healthy individuals with normal thyroid function tests. The polymerase chain reaction with sequence specific primers (PCR-SSP) method was used for HLA typing. Results: Frequencies of HLA-A*68 (15.6% vs. 4.2%, p=0.004) and B*08 (8.8% vs. 2.5, p=0.030) were significantly higher in patients with GD compared with healthy controls. No patients with GD had HLA-A*33, whereas it was found in 7.0% of the controls (p=0.011). HLA-DQB1*0201 was significantly less frequent among patients with GD (15.6% vs. 26.8%, p=0.040). Additionally, patients with GD were significantly less bound to have HLA-DQA1*0201 (6.2% vs. 15.1%, p=0.045). Concerning allelic distributions, no noticeable difference was found between GD patients with and without Graves’ ophthalmopathy (p>0.05 in all cases). Conclusion: In the Iranian population, HLA-A*68 and -B*08 confer susceptibility to GD, whereas HLA-A*33, -DQB1*0201, and -DQA1*0201 appear to have protective roles.
Parham Nejati; Marzieh Attar; Maryam Rahimian; Davood Fathi; Majid Shahbazi
Volume 14, Issue 3 , September 2017, , Pages 231-239
Abstract
Background: Multiple sclerosis (MS), as a multifactorial autoimmune disease with complex genetic basis, causes demyelination in the central nervous system via cytokine responses to myelin antigens. Myelin basic protein (MBP) is the main protein component of the myelin sheath. HLA-DRB (human leukocyte ...
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Background: Multiple sclerosis (MS), as a multifactorial autoimmune disease with complex genetic basis, causes demyelination in the central nervous system via cytokine responses to myelin antigens. Myelin basic protein (MBP) is the main protein component of the myelin sheath. HLA-DRB (human leukocyte antigen-DR beta) alleles, particularly HLA-DRB1*1501, may be of significance in the pathogenesis of MS. Objective: To examine the association of HLA-DRB1*1501 alleles and MBP VNTR (variable number tandem repeat) polymorphism with the MS susceptibility in Iranian population. Methods: Genomic DNA was extracted from peripheral blood. The alleles were determined by the Polymerase Chain Reaction (PCR) method in 259 MS patients and 312 healthy control individuals and analyses were carried out using Fisher's exact test. Results: The frequencies of MBP VNTR genotypes (AA, AB and BB) were 47%, 42% and 11% among patients, and 45%, 43% and 12% in control subjects, respectively. HLA-DRB1*1501 allele was more frequent among patients than healthy individuals (OR=1.65, P=0.0045). The frequency of allele A and genotype A/A was significantly higher among HLA-DRB1*1501 positive patients (61% and 32%) than controls (46% and 19%) (OR=1.88, P=0.0013; A/A vs. B/B: OR=5.09, P=0.0004). The two-locus analysis of the interaction between the MBP VNTR polymorphism and the HLA-DRB1 allele showed that the HLADRB1* 1501/A haplotype was more frequent among MS patients than the healthy controls. Conclusion: The interaction between the HLA-DRB1*1501 allele and MBP gene may be considered as a predisposing factor in the development and pathogenesis of MS in the case of gene-gene interaction.
Vamsi Lavu; Vettriselvi Venkatesan; Priyanka Venugopal; Bhaskar Venkata Kameswara Subrahmanya Lakkakula; Solomon Franklin Durairaj Paul; Kumarasamy Peria; Suresh Ranga Rao
Volume 14, Issue 1 , March 2017, , Pages 51-58
Abstract
Background: Cytokines are suggested to play a role in periodontitis. Objective: To determine and compare the levels of Interleukin-1 beta (IL-1β) and Tumor necrosis factor alpha (TNF-α) in gingival crevicular fluid (GCF) samples amongst healthy individuals and those with chronic periodontitis. ...
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Background: Cytokines are suggested to play a role in periodontitis. Objective: To determine and compare the levels of Interleukin-1 beta (IL-1β) and Tumor necrosis factor alpha (TNF-α) in gingival crevicular fluid (GCF) samples amongst healthy individuals and those with chronic periodontitis. Further to compare the GCF cytokine levels in three genotype classes defined by the respective gene polymorphisms. Methods: The study was conducted on 41 chronic periodontitis patients and 40 healthy volunteers. IL-1β and TNF-α were quantified in GCF by cytometric bead array. DNA was extracted from peripheral blood samples and genotyping of IL1B +3954C/T (rs1143634) IL1B -511G/A (rs16944), TNFA -1031T/C (rs1799964) and TNFA -863C/A (rs1800630) polymorphisms were performed using Sanger sequencing and Taqman SNP genotyping assays methods. Results: Both IL-1β and TNF-α levels were significantly higher in chronic periodontitis group compared to the controls. IL-1β and TNF-α levels did not significantly differ in genotype classes of the respective polymorphism (IL1B -511G/A, TNFA -1031T/C and TNFA -863C/A). However, individuals with CT genotype of IL1B +3954C/T showed higher levels of IL-1β in the gingival crevicular fluid (ANOVA p<0.05). Conclusion: The results of this study revealed the presence of higher levels of IL-1β and TNF-α in subjects with periodontitis and genetic control of IL-1β levels in our samples of Indians.
Mohammadrasul Zareinejad; Afshin Samiei; Behnaz Valibeigi; Tahereh Gholami; Soheila Zareifar; Zahra Amirghofran
Volume 14, Issue 1 , March 2017, , Pages 59-72
Abstract
Background: Interleukin (IL)-23 has an important role in tumor immune regulation. Objective: To investigate the possible association of interleukin-23 receptor (IL23R) gene variants rs1884444, rs10889677 and rs11209026 with development of acute lymphoblastic leukemia (ALL). Methods: The IL23R variants ...
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Background: Interleukin (IL)-23 has an important role in tumor immune regulation. Objective: To investigate the possible association of interleukin-23 receptor (IL23R) gene variants rs1884444, rs10889677 and rs11209026 with development of acute lymphoblastic leukemia (ALL). Methods: The IL23R variants were studied in 164 ALL patients and compared to 175 healthy controls by polymerase chain reaction-restriction fragment length polymorphism. The relationship between these variants and clinical and laboratory features of the patients and response to therapy were evaluated. Results: No significant differences in genotype and allele frequencies existed between patients and controls. The rs1884444TG genotype was significantly lower in patients who relapsed (24.2%) compared to those without relapse (55.9%, p=0.006). Fewer patients who relapsed had evidence of the G allele (P=0.034). The TG genotype was associated with a longer complete remission at1804±116 days compared to other genotypes (<1217 days, p=0.028), however this result was not significant in multivariate analysis. The rs10889677 AA genotype and A allele was associated with age (p<0.041) and platelet number (p=0.03) in precursor-B cell ALL (B-ALL) patients. Both occurred more frequently in patients aged 2-10 years (63.6% and 66%, respectively) and in those with platelets >100×103μL (68.4% and 52.4%, respectively). Conclusion: Our findings showed a lack of association of the studied polymorphisms with the risk of ALL. The influence of the rs1884444 polymorphism on relapse rate and association of rs10889677 AA genotype with favorable prognostic factors suggest the influence of the studied polymorphisms on ALL response to therapy and prognosis.
Fahimah Anvari; Feryal Dabagh-Gorjani; Mohammad-Sadegh SoltaniZangbar; Eskandar Kamali-Sarvestani; Zahra Malek-Hosseini; Behrouz Gharesi-Fard
Volume 12, Issue 2 , June 2015, , Pages 117-128
Abstract
Background: Pre-eclampsia (PE) is one of the most important and life-threatening pregnancy disorders that affect at least 3-5% of all pregnancies. Imbalance in helper T cell functions may play a role in predisposing to PE or severity of the disease. Elevated frequencies of Th17 cells in the peripheral ...
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Background: Pre-eclampsia (PE) is one of the most important and life-threatening pregnancy disorders that affect at least 3-5% of all pregnancies. Imbalance in helper T cell functions may play a role in predisposing to PE or severity of the disease. Elevated frequencies of Th17 cells in the peripheral blood of PE patients have been reported. Several single nucleotide polymorphisms (SNP) within IL-17 gene have been identified that may affect the IL-17 production. Objectives: To investigate the association between IL-17A (-197A/G) and IL-17F (+7488T/C) gene polymorphisms and susceptibility to PE in a group of Iranian women. Moreover, to study any correlation of the polymorphisms data with the level of IL-17, at mRNA level in the paternal and maternal parts of the placentas and also at protein level in the peripheral and placental blood samples. Methods: A group of 261 PE patients and 278 age-matched healthy women with at least two previous normal pregnancies formed the cases and controls of this study. IL-17A (-197A/G) and IL-17F (+7488T/C) polymorphisms were genotyped using PCR-RFLP method. The protein level of IL-17A was assessed in the sera of 40 PE and 40 healthy women using ELISA method and mRNA expression was also measured in placental samples of 19 PE and 19 control women using Q-PCR technique. Results: Statistical analysis indicated that there were no differences in genotype, allele or haplotype frequencies regarding the studied SNPs between cases and controls. The level of IL-17A was elevated in the placental blood and the fetal tissue at protein and mRNA levels (p< 0.009 and p<0.000, respectively) in PE as compared with the healthy women. Conclusions: The effect of IL-17 cytokine in pre-eclampsia is not due to the studied cytokine polymorphisms but local production of IL-17 might have an effect on the predisposition to the disease.
Sadaf Asaei; Manoochehr Rasouli; Ali Moravej
Volume 10, Issue 3 , September 2013, , Pages 158-166
Abstract
Background: Increased levels of interleukin-8 (IL-8) and interleukin-6 (IL-6) in acute human brucellosis have been reported. Previous studies have shown that the production and level of IL-6 and IL-8 cytokines are associated with the polymorphism of the encoding genes. Objective: To investigate the probable ...
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Background: Increased levels of interleukin-8 (IL-8) and interleukin-6 (IL-6) in acute human brucellosis have been reported. Previous studies have shown that the production and level of IL-6 and IL-8 cytokines are associated with the polymorphism of the encoding genes. Objective: To investigate the probable association between IL-6 (-174 C/G) and IL-8 (-251 A/T) gene polymorphisms and susceptibility/resistance to brucellosis. Methods: The patient group included 196 patients suffering from Brucella infection and the control group consisted of 82 healthy animal husbandmen from the same geographical area. IL-8 (-251 A/C) and IL-6 (-174 C/G) gene polymorphisms were analyzed by PCR-RFLP and Allele Specific PCR (AS-PCR) respectively. Results: The frequency of -251 IL-8 AA genotype was significantly lower in the controls compared with that of the patients (p=0.0051), while the frequencies of other genotypes (AT and TT) and alleles (A and T) were not significantly different among the participants. No association was found between IL-6 (-174 C/G) polymorphism and brucellosis. Conclusion: This study indicates that the IL-8 -251 AA genotype may be considered as a genetic susceptibility factor for brucellosis.
Nasrollah Erfani; Faezeh Moghaddasi-Sani; Mahboubeh Razmkhah; Mohammad Reza Haghshenas; Abdolrasoul Talaei; Abbas Ghaderi
Volume 9, Issue 4 , December 2012, , Pages 226-233
Abstract
Background: CCL22/MDC is a CC chemokine with a critical role in regulation of the immune balance in physiological condition. CCL22/CCR-4 ligation has been documented to participate in the migration of regulatory T (Treg) cells and Th2 lymphocytes to the site of breast tumors; circumstances that are known ...
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Background: CCL22/MDC is a CC chemokine with a critical role in regulation of the immune balance in physiological condition. CCL22/CCR-4 ligation has been documented to participate in the migration of regulatory T (Treg) cells and Th2 lymphocytes to the site of breast tumors; circumstances that are known to be associated with poor prognosis. Objective: To investigate the association of a single nucleotide polymorphism (SNP) in CCL22 gene; 16C/A (rs4359426; Asp2Ala), with susceptibility to breast cancer in a sample of Iranian population. Methods: 161 patients with pathologically confirmed breast carcinoma (mean age 49.3 ± 11.5 yrs) and 178 agematched healthy women (mean age: 49.3 ± 12.9 yrs) were studied. CCL22 genotypes were investigated by the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Data was verified by direct automated sequencing. Arlequin analysis showed no deviation from Hardy-Weinberg equilibrium. Results: The most frequent genotype in both patient and control groups was wild type CC genotype with frequency of 146 out of 161 (90.7%) among patients and 153 out of 178 (86.0%) in control group (p=0.24). The frequency of CA genotype was 15 (9.3%) and 23 (12.9%) in patients and controls, respectively (p=0.38). No AA genotype was observed among patients but this genotype was observed with the frequency of 2 out of 178 (1.1%) in control subjects. The minor allele frequency (MAF) was 0.07 in the population. Conclusion: No correlation was found between the investigated genotypes and clinicopathological characteristics of the patients. Conclusively, results of this investigation do not support the association of 16C/A SNP (rs4359426; Asp2Ala) in CCL22 gene with susceptibility to, and progression of, breast cancer in Iranian population.
Nasrollah Erfani; Mohammad Reza Haghshenas; Mohammad Ali Hoseini; Seyed Basi Hashemi; Bijan Khademi; Abbas Ghaderi
Volume 9, Issue 3 , September 2012, , Pages 188-198
Abstract
Background: Variations in Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) affect the expression and function of this protein. Objective: We aimed to investigate the association of +49 A/G (rs231775), +1822 C/T (rs231779) and +6230 A/G (CT60, rs3087243) genetic variations, as well as the merged haplotypes in ...
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Background: Variations in Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) affect the expression and function of this protein. Objective: We aimed to investigate the association of +49 A/G (rs231775), +1822 C/T (rs231779) and +6230 A/G (CT60, rs3087243) genetic variations, as well as the merged haplotypes in CTLA-4 gene with susceptibility to, or progression of head and neck cancer. Methods: Eighty patients with confirmed head and neck (HN) cancer (age 54.9 ± 16.1 years) and 85 healthy age/sexmatched controls (age 56.3 ± 12.4 years) were enrolled in the study. Genotypes were investigated by the PCR-RFLP method. Arlequin software package was used to check for Hardy-Weinberg equilibration, and to estimate the haplotypes. Results: At position +6230 A/G (CT60), AA genotype, as well as A allele was significantly decreased in patients with HN cancers than controls (18.8% vs. 40.7%, p=0.004; odds ratio=0.34, and 46.3% vs. 61.7, p=0.007; odds ratio=0.53%, respectively). Nearly the same results were obtained when we compared the subgroup of patients with squamous cell carcinoma of the HN (SCC-HN) with control subjects. The frequencies of genotypes and alleles at other positions were not significantly different between patients and controls, however ACG, GTA and GCA haplotypes emerged from three investigated loci occurred with significantly more frequencies in patients (p<0.0001), while ACA and GTG haplotypes were more frequent among controls (p<0.0001). Significant differences of haplotypes, genotypes and alleles frequencies resisted the Bonferroni correction. Conclusion: Our results suggest that CT60 A allele, as well as ACA and GTG haplotypes in CTLA-4 gene may have protective roles against HN cancer in Iranian population, while ACG, GTA and specially GCA haplotypes may render susceptibility.
Abbas Ghaderi
Volume 8, Issue 3 , September 2011, , Pages 127-149
Abstract
Gene association studies are less appealing in cancer compared to autoimmune diseases. Complexity, heterogeneity, variation in histological types, age at onset, short survival, and acute versus chronic conditions are cancer related factors which are different from an organ specific autoimmune disease, ...
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Gene association studies are less appealing in cancer compared to autoimmune diseases. Complexity, heterogeneity, variation in histological types, age at onset, short survival, and acute versus chronic conditions are cancer related factors which are different from an organ specific autoimmune disease, such as Grave’s disease, on which a large body of multicentre data is accumulated. For years the focus of attention was on diversity and polymorphism of major histocompatibility complex in respect to human diseases specially the autoimmune diseases, but in recent years, access to other human gene sequences prompted investigators to focus on genes encoding the immune regulatory proteins such as the co-stimulatory, adhesion molecules, cytokines and chemokines and their receptors. Among them, CTLA4 (CD152) has been in the centre of attention for its pivotal role in autoimmunity and cancer. Although not fully understood, CTLA4 with no doubt plays an important role in the maintenance of the immune response by its expression on activated and regulatory T cells. CTLA4 (Gene ID:1493, MIM number:123890) has many variants and polymorphic forms, some present in regulatory positions, some in 3' UTR and the most important one in the leader sequence (+49 A/G). As a pivotal regulatory element of the immune responses magnitude, CTLA4 could be considered as a two-blade knife, for which only the optimal expression ensures an effective, but at the same time, safe immune response. It can accordingly be speculated that CTLA4 alleles associated with extraordinary expression could make a person more susceptible to tumor growth and/or progression. On the other hand, alleles associated with a compromised CTLA4 expression/function may accelerate the formation and/or manifestation of inflammatory autoimmune disorder. I hypothesized a spectrum of the functional dichotomy of CTLA4 SNPs diverging from autoimmunity to cancer. To examine these hypotheses, results from previously published investigations on CTLA4 polymorphisms together with the work done by our own group are discussed in details. Because the most published data are about the polymorphism at position +49, I concentrated on this position; however the data regarding other SNPs are also included for comparison. To support the significance of CTLA4 gene variation in these two major human diseases evidences from organ transplantation are also included. As will be discussed in the manuscript, our work and reports by others from a normal population perspective support the hypothesis that individuals inheriting a GG genotype at position +49, for which lower CTLA4 expression has been extensively suggested, are more susceptible for developing autoimmune disorders and those with AA genotype, with an existence of a state of self-tolerance, may have a higher chance of developing cancer. CTLA4 SNPs may accordingly be considered as a crucial element, along with other known or yet unknown mechanisms, in keeping the immune balance in predisposed individuals to cancer and autoimmunity. Although an spectrum line can be drawn between autoimmunity and cancer by considering published data regarding CTLA4 +49 polymorphism, the extreme functional dichotomy of this SNP appears to be more complex and difficult to understand, but there is no doubt that the future investigations will resolve most ambiguities.
Gholam ALi Yousefipour; Mohammad Reza Haghshenas; Sara Yahyazadeh; Nasrollah Erfani
Volume 8, Issue 2 , June 2011, , Pages 90-95
Abstract
Background: Myasthenia gravis (MG) is the most common disorder of neuromuscular junction in which autoantibodies develop against nicotinic acetylcholine receptor for unknown reasons. The association of immunomodulator genes with different autoimmune disease has been studied in recent years. Objective: ...
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Background: Myasthenia gravis (MG) is the most common disorder of neuromuscular junction in which autoantibodies develop against nicotinic acetylcholine receptor for unknown reasons. The association of immunomodulator genes with different autoimmune disease has been studied in recent years. Objective: The aim of this study was to investigate correlation between a genetic variation in Stromal Cell Derived Factor-1 (SDF1) and susceptibility to MG in an Iranian population. Methods: Genotyping of SDF1 at position 801 G/A was performed by Polymerase Chain Reaction-Restriction Length Polymorphism (PCR-RFLP) in 87 patients with confirmed myasthenia gravis and 261 normal control subjects. Results: No statistically significant differences were observed in the frequencies of genotypes and alleles between patients and controls (p>0.05). Furthermore, no significant differences in the genotype distribution were found between the cases with different stages (p>0.05). Conclusion: Our data suggest that the SDF1 gene polymorphism at position 801 G/A is not associated with myasthenia gravis
Shohreh Farshad; Manoochehr Rasouli; Akram Jamshidzadeh; Ayda Hosseinkhani; Aziz Japoni; Abdolvahab Alborzi; Alireza Taghavi; Hossein Kazemi Asl; Reza Ranjbar
Volume 7, Issue 2 , June 2010, , Pages 96-108
Abstract
Background: Previous studies imply that IL-1 and IL-8 gene variations may play a crucial role in the genetic predisposition to different gastric disorders upon H. pylori infection. Objective: The aim of this study was to determine the potential association between the prevalence of certain polymorphic ...
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Background: Previous studies imply that IL-1 and IL-8 gene variations may play a crucial role in the genetic predisposition to different gastric disorders upon H. pylori infection. Objective: The aim of this study was to determine the potential association between the prevalence of certain polymorphic sites and the risk of gastric disorders in Iranian population. Methods: One hundred and forty three unrelated individuals with different gastric disorders and 374 normal individuals with no gastric disorders and with a negative serology test for H. pylori (control group) were studied for the association between IL-1β (+3953 C/T) and IL-8 (-251 A/T) gene polymorphisms and H. pylorimediated gastritis and gastric ulcer. An analysis of genotype frequency for these genes was performed using RFLP-PCR. Results: Based on the data obtained from culture and pathologic findings, the patients were classified into three subpopulations: H pylori+ non-ulcerative gastritis+, H. pylori+ ulcerative gastritis+ and H. pylori- non-ulcerative gastritis+. A significantly higher frequency of TT genotype (p=0.02) in IL-1β +3953 in H. pylori+ ulcerative gastritis+ was revealed compared to the control group. There were no significant differences among other subpopulations. No significant differences in allele and genotype frequencies of IL-8 (-251A/T) were found among the patients. Conclusion: The data suggest that TT genotype in IL-1β +3953 may be a major contributing genetic risk factor for H. pylori induced gastric ulcer. Moreover, the role of other bacterial and host response factors, such as bacterial adherence peptides, host chemokines, and genes involved in gastric acid secretion, must be further investigated in different ethnic populations.
Eskandar Kamali-Sarvestani; Hadi Farsiani; Michel Shamoon Pour; Abdulah Bazargani; Kamran Lankarani; Ali-Reza Taghavi; Mehdi Saberifiroozi
Volume 4, Issue 3 , December 2007, , Pages 155-160
Abstract
Background: Polymorphisms in the immune related genes are important in the clinical outcome of Helicobacter pylori infection. Myeloperoxidase -463 G/A polymorphism has been shown to reduce enzyme expression and activity. Objective: the aim of the present study is to investigate the association of myeloperoxidase ...
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Background: Polymorphisms in the immune related genes are important in the clinical outcome of Helicobacter pylori infection. Myeloperoxidase -463 G/A polymorphism has been shown to reduce enzyme expression and activity. Objective: the aim of the present study is to investigate the association of myeloperoxidase G-463A polymor-phism with clinical outcome of Helicobacter pylori infection. Methods: two hundred and eighty five patients with positive culture of Helicobacter pylori from their gastric biopsies are included in this study. Human leukocyte DNA was extracted using salting out method and myeloperoxidase G-463A polymorphism was investigated by PCR-RFLP. All clinicopathological data were collected from individual records. Results: When the patients were categorized according to the high (GG) and low + intermediate (AG+AA) genotypes of myeloperoxidase producers, there was a significant association between myeloperoxidase G-463A genotypes and clinical outcome of Helicobacter py-lori infection (p=0.006). In search for combined effect of cagA status and myeloperoxi-dase genotypes on clinical presentations, only in cagA- Helicobacter pylori infected pa-tients a significant association between myeloperoxidase genotypes and clinical out-come was found (p=0.0001). Also this association was found only in patients infected with vacA s1m1 genotype (p=0.008). Conclusions: Our findings suggest that the mye-loperoxidase G-463A polymorphism is a host genetic factor which determines the clini-cal outcome of Helicobacter pylori infection. Moreover, the combination of host and bacterial genetics could provide a better understanding of clinical outcome after infec-tion with Helicobacter pylori.
Raja Rajalingam
Volume 4, Issue 2 , June 2007, , Pages 61-78
Abstract
Natural killer (NK) cells are a subset of lymphocytes which play a crucial role in early innate immune response against infection and tumor transformation. Furthermore, they secrete interferon-γ (IFN-γ) and tumor necrosis factor (TNF) prompting adaptive immu-nity. NK cells distinguish the ...
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Natural killer (NK) cells are a subset of lymphocytes which play a crucial role in early innate immune response against infection and tumor transformation. Furthermore, they secrete interferon-γ (IFN-γ) and tumor necrosis factor (TNF) prompting adaptive immu-nity. NK cells distinguish the unhealthy cells from the healthy ones through an array of cell-surface receptors. Human NK cells use inhibitory and activating killer cell Ig-like receptors (KIR) as primary probe to discriminate between healthy and unhealthy cells. The inhibitory KIRs recognize HLA class I molecules and trigger signals that stop NK killing. The activating KIRs are believed to recognize the determinants associated with infections and tumors, and trigger signals that activate NK killing. Therefore, the effec-tor function of a given NK cell depends upon the receptors that it expresses and ligands that it recognizes on the targets. Genes encoding KIRs and HLA ligands are located on different chromosomes, and vary in number and type. The independent segregation of KIR and HLA genes results in variable KIR-HLA combinations in individuals, which may determine the individual’s immunity and susceptibility to disease.
Alireza Nikseresht; Mohammad Ali Azizi; Behrouz Gharesi-Fard; Eskandar Kamali Sarvestani
Volume 3, Issue 3 , September 2006, , Pages 136-141
Abstract
Background: Multiple Sclerosis (MS), the most common demyelinating disease of the CNS, is immunologically mediated in genetically susceptible individuals. Receptors for the Fc fragment of IgG (FcγR) might induce inflammatory responses through linking the humoral and cellular immune responses by ...
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Background: Multiple Sclerosis (MS), the most common demyelinating disease of the CNS, is immunologically mediated in genetically susceptible individuals. Receptors for the Fc fragment of IgG (FcγR) might induce inflammatory responses through linking the humoral and cellular immune responses by targeting immune complexes to effector cells. Polymorphisms in some FcγR genes are associated with various infectious and autoimmune diseases, probably due to their effects on different binding capacities of encoded receptors for IgG containing immune complexes. Objective: To investigate the importance of FcγR polymorphisms in susceptibility to MS. Method: One hundred and fifty MS patients and 136 age and sex matched controls were genotyped for FcγRIIA and FcγRIIIA gene polymorphisms using PCR-RFLP method. Result: The allelic and genotypic frequencies of the FcγRIIA and FcγRIIIA did not differ significantly between the MS patients and controls. There was no association between allelic polymorphism of FcγRIIIA and severity of disease based on Expanded Disability Status Scale (EDSS) score. However, significant association between inherited FcγRIIA genotype and disease activity (p=0.001) or progression index was revealed (p=0.014). EDSS values showed that FcγRIIA (H/H) and (H/R) genotypes were associated with a lower EDSS score in relapsing-remitting MS and in the total MS population (P=0.001) but not (R/R) genotype. Conclusion: Considering the detrimental role of autoantibodies in the pathogenesis of MS, our results suggest that the inherited FcγRIIA alleles could affect the severity of MS by influencing the clearance rate of immune complexes and autoantibodies. The results of the present study add the FcγRIIA gene to the gene networks which determine the severity of MS in southern Iran.
Hossein Abdolrahim-Zadeh; Niloufar Hakkakian; Reza Asadollahi; Behrouz Gharesifard; Jamal Sarvari; Eskandar Kamali-Sarvestani; Abdolrasoul Talei
Volume 2, Issue 3 , September 2005, , Pages 158-165
Abstract
Background: IL-10 is an anti-inflammatory cytokine which is involved in tumorigenesis. Over production of IL-10 and elevated number of IL-10 generating mononuclear cells in breast tumor tissue has already been shown. Objective: To determine the association of IL-10 promoter polymorphisms with increased ...
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Background: IL-10 is an anti-inflammatory cytokine which is involved in tumorigenesis. Over production of IL-10 and elevated number of IL-10 generating mononuclear cells in breast tumor tissue has already been shown. Objective: To determine the association of IL-10 promoter polymorphisms with increased risk of breast cancer and its association with breast cancer prognostic factors. Methods: Peripheral blood samples from 275 female breast cancer patients and 320 cancer free controls were used to detect three single nucleotide polymorphisms in IL-10 promoter region ( -1082, -819, -592 ) by PCR method. Results: The frequency of genotypes and alleles of three mentioned regions of IL-10 promoter and their haplotypes (GCC, ATA, and ACC) showed no statistically significant difference between patients and controls. In the case of prognostic factors, progesterone receptor (PR) status exhibited significant relation with -1082 genotypes (P=0.03) and haplotypes (P=0.02). -1082 AA genotype was associated with negative PR expression whereas AG and GG genotypes of this site were positively associated with PR expression. Similarly GCC haplotype correlated with positive PR expression and ATA and ACC with negative PR expression. Conclusion: The data of this study showed that IL-10 promoter gene polymorphisms may not be considered as one of the risk factors for breast cancer in Iranian patients.
Mohammad Javad Fattahi; Abdul Mohammad Pezeshki; Maryam Emad; Mohammad Hosein Lohrasb; Azra Shamseddin; Abbas Ghaderi; Mehrnoosh Doroudchi
Volume 2, Issue 2 , June 2005, , Pages 97-102
Abstract
Background: Vitiligo is an acquired skin disorder that selectively destroys melanocytes in epidermis with an unknown etiology. Objective: To investigate the exon 1 A49G polymorphism of cytotoxic T lymphocyte antigen-4 (ctla-4) gene in vitiligo patients. Methods: The A49G polymorphism was ...
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Background: Vitiligo is an acquired skin disorder that selectively destroys melanocytes in epidermis with an unknown etiology. Objective: To investigate the exon 1 A49G polymorphism of cytotoxic T lymphocyte antigen-4 (ctla-4) gene in vitiligo patients. Methods: The A49G polymorphism was detected by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method in 101 patients and 208 normal healthy age/ethnicity matched individuals. Results: The frequencies of heterozygote genotypes in patients and controls were found to be 42 (41.6%) of 101 and 85 (40.9%) of 208, respectively. The frequencies of homozygote A and G genotypes were 49 (48.5%) and 10 (9.9%) in 101 patients, whereas, these frequencies in 208 control individuals were 103 (49.5%) and 20 (9.6%), respectively. There was no significant difference between the genotype (P = 0.98) and allele (P = 0.86) frequencies of A49G polymorphism in patients and normal healthy individuals. Conclusion: Our results indicate that in contrast to several immune mediated disorders, there is no association between ctla-4 A49G gene polymorphism and vitiligo.
Ali Akbar Amirzargar; Abdol Ali Danesh; Farideh Khosravi; Mohammad Hossein Niknam; Behrouz Nikbin
Volume 1, Issue 2 , September 2004, , Pages 125-129
Abstract
Background: Pulmonary tuberculosis (PTB) has recently become a major problem in developed countries especially in immune compromised HIV infected individuals. Cytokines, their genes and receptors have been implicated in the protective immunity, pathophysiology and development of tuberculosis. ...
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Background: Pulmonary tuberculosis (PTB) has recently become a major problem in developed countries especially in immune compromised HIV infected individuals. Cytokines, their genes and receptors have been implicated in the protective immunity, pathophysiology and development of tuberculosis. Material & Methods: In the present study the genotype frequencies of a number of polymorphic genes coding for cytokines or for cytokine receptors have been investigated in a case control study including a group of 40 Iranian PTB patients and 40 healthy individuals. The allelic polymorphism of cytokines SNPs were analyzed according to the protocols of the cytokine component designed for the 13th IHW by the Heidelberg University group. Using PCR-SSP method the following cytokine genes have been determined: IL-1 ¿ (T/C –889), IL-1¾ (C/T +3962), IL-1R (C/T pstI 1970), IL-1RA ( T/C mspaI 1100), IL-4RA (G/A +1902), IL- 12 (C/A –1188), TGF- ¾ (C/T codon 10, G/C codon 25), TNF-¿ (G/A –308, G/A –238), IL-2 (T/G –330 G/T +166), IL-4 (T/G –1098, T/C –590, T/C –33), IL-6 (G/C –174, G/A nt 560), IL-10 (G/A –1082, C/T –819, C/A –592). Results: From IL-1R cluster (pro- inflammatory cytokines) a positive significant association was found at position pstI 1970 C/T polymorphism where the C allele was over presented in the PTB patients (60% vs. 37.5%, P = 0.04). A significant negative association at codon 10 TGF- ¾ C/T polymorphism has also been shown in our patients, where the T allele was not detected in the patients but 10% of the control subjects expressed this allele (Fisher exact test, P = 0.05). At this codon allele T (Leucine substitution) is associated with high TGF- ¾ production. For TNF ¿ an insignificant tendency was found at position -308 A/G polymorphism where the G allele carried by 80% of cases and 65% of controls (P = 0.07). At position -238 a negative association was found at the GA polymorphism (10% vs. 25%, P = 0.07). For IL-6 an insignificant positive association at position -174 C/G polymorphism, G allele (57.5% vs. 37.5, P = 0.07) was found. At the other cytokine genes no specific association were found. Conclusion: In conclusion it is suggested that C allele at position pstI 1970 of IL-1 cluster increases and T allele at codon 10 of TGF- ¾ decreases in PTB patients.
Ali Rafinejad; Mohammad Hossein Niknam; Ali Akbar Amirzargar; Farideh Khosravi; Forouzan Karimi; Bagher Larijani
Volume 1, Issue 2 , September 2004, , Pages 130-132
Abstract
Background: Type 1 Diabetes (T1D) is a chronic and progressive autoimmune disorder. Cytokines play a critical role in the pathogenesis of T1D. Objective: IFN-¹ polymorphism was investigated in T1D and compared with normal controls. Methods: Thirty patients suffering from T1D and 40 ...
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Background: Type 1 Diabetes (T1D) is a chronic and progressive autoimmune disorder. Cytokines play a critical role in the pathogenesis of T1D. Objective: IFN-¹ polymorphism was investigated in T1D and compared with normal controls. Methods: Thirty patients suffering from T1D and 40 normal controls were studied simultaneously using PCR technique. IFN- ¹ gene was evaluated at position 5’UTR +5644. Results: There was a significant difference between patient and control groups in TT genotype (P<0.05). Conclusion: In this study, we found a negative association between IFN-¹ gene at position 5’UTR +5644 and T1D in Iranian patients pointing to T allele as a protective factor against T1D.
