期刊
INTERNATIONAL JOURNAL OF IMMUNOGENETICS
卷 45, 期 1, 页码 1-7出版社
WILEY
DOI: 10.1111/iji.12347
关键词
arthritis; autoimmune; cohort study; disease; HLA polymorphism; immunology
Rheumatoid arthritis (RA) is a complex, multifactorial, systemic autoimmune disease. Reports are suggestive of the role of HLA especially HLA-DRB1 alterations in RA pathogenesis. Existing data involving different geographical populations on the role of alterations in specific locus of HLA-DRB1 in RA susceptibility and severity are equivocal, with no data available from ethnically distinct North-east Indian population, where RA cases are alarmingly increasing. This study aimed to evaluate the association of HLA-DRB1 gene SNPs (rs13192471, rs660895 and rs6457617) with susceptibility and severity of RA in an ethnically distinct North-east Indian population. Whole blood was collected from clinically characterized RA cases (satisfying the American College of Rheumatology 1987 criteria) (n=123) and community-based age and sex-matched healthy controls (n=156) with informed consent. The HLA-DRB1 SNP analysis was performed for all the RA and control cases using ARMS-PCR using case and control genomic DNA as template. Statistical analysis was performed by SPSSv13.0 software. The HLA-DRB1 rs660895 showed both wild (AA) and heterozygote (AG) genotype but the heterozygote allele was found to be associated with reduced risk of RA compared to controls [OR=0.531, p=.024]. The difference in distribution of rs6457617 polymorphism between RA and control cases was comparable [OR=0.525, p=.079]. Significantly higher distribution of variant rs13192471 genotype was observed in RA cases (69.92%) compared to controls (46.75%) (p<.001) and was associated with increased risk of susceptibility to RA [OR=2.576, p<.001] compared to controls, as well as progression to severity in RA cases [OR=2.404, p=.048]. Combinatorially also, the presence of rs13192471 variant genotype was associated with increased risk of RA susceptibility [OR=8.267, p=.026] and RA severity [OR=3.647, p=.280]. Alterations in HLA-DRB1 are associated with RA susceptibility. HLA-DRB1 rs13192471 SNP plays a critical role in RA susceptibility and severity in North-east Indian cases and has prognostic significance in RA.
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