Iranian Journal of Immunology

Association of three functional polymorphisms in the NLRP3 gene with susceptibility to rheumatoid arthritis in Iranian population

Document Type : Original Article

Authors

Mehrdad Nasrollahzadeh Sabet 1
Navid Nasrabadi 2
Zahra Jalili 3
Bahram Pakzad 4
Saeideh Davar 5
Naeim Ehtesham 6
Sima Jafarpour 6
Meysam Mosallaei 6
Emran Esmaeilzadeh 7

1 School of Medicine, Aja University of Medical Science, Tehran, Iran.

2 Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 School of Medicine, Lorestan University, Khuram Abad, Iran

4 Division of Rheumatology, Department of Internal Medicine, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran.

5 Department of Epidemiology and Biostatistics, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran

6 Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable disease.

7 School of Medicine, Aja University of Medical Science, Tehran, Iran

https://doi.org/10.22034/iji.2021.89507.1950
Abstract
Background: Rheumatoid arthritis (RA) is a complex systemic autoimmune disorder with multifactorial nature. Numerous previous studies have shown that several genes are involved in the pathogenesis and increased risk of RA. The Nod-like receptor pyrin domain containing 3 (NLRP3) is involved in the regulation of innate immunity and its upregulation has previously been reported in RA. Objective: To evaluate the correlation between 3 functional polymorphisms of NLRP3 and its gene expression and RA risk. Method: One hundred and fourteen patients with RA and 120 healthy participants were recruited to this case-control study. Genotyping of rs4612666 (intronic variant), rs10754558 (3UTR variant), and rs6672995 (downstream variant) were performed applying the real‑time polymerase chain reaction high‑resolution melting (HRM) method. Results: Based on logistic regression analysis, subjects with CC genotype and C allele in rs4612666 had increased risk of RA (OR for CC genotype= 3.10; 95%CI [1.78-8.26]/ OR for C allele= 2.00; 95%CI [1.45-3.10]). Furthermore, in the patient groups, there was a significant relationship between the concentration of C-reactive protein (CRP) and rs4612666 and rs10754558 polymorphism (p < 0.05). Besides, our results revealed no significant association between the genotype and allele frequency of rs10754558 and rs6672995 and the risk of RA (P> 0.05). Conclusion: Our findings propose a significant association between rs4612666 polymorphism and increased risk of RA in the Iranian population. Moreover, rs4612666 and rs10754558 were correlated with disease activity.

Keywords

Arthritis
Genotypes
Inflammasome
NLRP3 Gene
Rheumatoid
Single Nucleotide Polymorphism
Iranian Journal of Immunology
Volume 18, Issue 3
Summer 2021
Pages 249-258

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