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

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