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Association of MICA‐129 polymorphism and circulating soluble MICA level with rheumatoid arthritis in a south Indian Tamil population
Author(s) -
Mariaselvam Christina M.,
Boukouaci Wahid,
Charron Dominique,
Krishnamoorthy Rajagopal,
Tamouza Ryad,
Misra Durga P.,
Negi Vir S.
Publication year - 2018
Publication title -
international journal of rheumatic diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 41
eISSN - 1756-185X
pISSN - 1756-1841
DOI - 10.1111/1756-185x.13138
Subject(s) - genotype , rheumatoid arthritis , medicine , immunology , haplotype , odds ratio , nkg2d , allele , pathogenesis , polymorphism (computer science) , gene , biology , genetics , cytotoxic t cell , in vitro
Rheumatoid arthritis ( RA ) is a clinically heterogeneous chronic inflammatory disorder characterized by synovitis leading to joint destruction. Both genetic and environmental factors are involved in the pathogenesis of RA . Significant dysregulation of NKG 2D, an activating receptor of natural killer and certain autoreactive T cells as well as its ligand major histocompatibility complex class I chain–related gene A ( MICA ) has been implicated in perpetuating the pathology of RA . Since the genetic polymorphism in MICA gene ( MICA ‐129 met/val polymorphism at codon 129) is known to affect its binding affinity to NKG 2D, we explored its influence on RA susceptibility and disease severity. Methods The MICA ‐129 met/val polymorphism was examined in 270 patients with RA and 232 healthy controls by TaqMan 5′‐nuclease assay. Serum soluble MICA ( sMICA ) was measured in a subset of 89 patients and 80 controls by enzyme‐linked immunosorbent assay. Results We observed that the frequency of MICA ‐129 val allele (73% vs . 65%, P c = 0.006, odds ratio = 1.48, 95% CI = 1.12–1.95) was higher in patients than in controls. sMICA levels were significantly higher in patients with RA than in controls ( P < 0.0001). sMICA levels were higher in patients with val/val genotype than in those with met/val or met/met genotype ( P = 0.03). The MICA ‐129 val/val genotype was associated with high titers of sMICA in patients with deforming RA phenotype ( P = 0.02), suggesting a role in determination of severity of RA. Conclusion MICA ‐129 val/val genotype, associated with higher levels of circulating sMICA , may influence disease susceptibility and associate with increased severity of RA in south Indian Tamils.