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Polymorphisms in the promoter region of iNOS predispose to rheumatoid arthritis in south Indian Tamils
Author(s) -
Negi V. S.,
Mariaselvam C. M.,
Misra D. P.,
Muralidharan N.,
Fortier C.,
Charron D.,
Krishnamoorthy R.,
Tamouza R.
Publication year - 2017
Publication title -
international journal of immunogenetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.41
H-Index - 47
eISSN - 1744-313X
pISSN - 1744-3121
DOI - 10.1111/iji.12315
Subject(s) - single nucleotide polymorphism , rheumatoid arthritis , nitric oxide synthase , immunology , genotype , inflammation , promoter , nitric oxide , allele , medicine , biology , genetics , gene , gene expression
Summary Nitric oxide synthase (NOS) catalyses the production of nitric oxide (NO) from L‐Arginine, which participates in diverse biological processes including inflammation and apoptosis. Macrophages, chondrocytes, osteoblasts and osteoclasts express inducible NOS (iNOS) at the site of synovial inflammation. NO produced at the inflamed joint may contribute to peri‐articular bone loss, mediate apoptosis and regulate Th1/Th2 balance in rheumatoid arthritis (RA). Variations in the promoter region of NOS gene regulate the nitric oxide synthase expression and iNOS (NOS2) polymorphisms have been associated with susceptibility to autoimmune disorders. Hence, this study was conducted to identify the possible contributions of NOS2 ‐1659G/A, ‐1026C/A, ‐277A/G promoter polymorphisms towards development of RA in South Indian Tamils. A total of 242 (219 females, 23 males) patients with RA (mean age 41.2 ± 10.9 years, disease duration 8.5 ± 4.3 years) and 279 age‐ and sex‐matched healthy individuals of South Indian Tamil ethnicity were genotyped for NOS2 ‐1659C/T, ‐1026G/T and ‐277A/G promoter polymorphisms by TaqMan chemistry. Nature of disease (erosive or nonerosive), the presence of extra‐articular manifestations, seropositivity for rheumatoid factor and anticyclic citrullinated peptide, serum C‐reactive protein (CRP) level and response to therapy were assessed for all patients. The three single nucleotide polymorphisms (SNPs) were in Hardy–Weinberg equilibrium. The frequency of GG genotype and G allele of NOS2‐277 was higher in patients ( p c = 5.7 × 10 −9 , OR = 6.09, 95% CI = 3.09–12.8 and p c = 4 × 10 −13 , OR = 2.37, 95% CI = 2.06–3.62, respectively) compared to controls. Similarly, the frequency of NOS2‐1026 (rs2779249) GT genotype and the T allele was higher in patients with RA ( p c = .01, OR = 1.61, 95% CI = 1.09–2.36, and p c = .04, OR = 1.40, 95% CI = 1.02–1.91, respectively). However, no significant difference in frequency of NOS2‐1659C/T polymorphism was observed between patients and controls. None of the studied SNPs were associated with erosive disease, seropositivity or extra‐articular manifestations. The ‐277A/G and ‐1026 G/T promoter polymorphisms in iNOS may confer susceptibility to RA in South Indian Tamils.