Associative role of HLA ‐ DRB 1 SNP genotypes as risk factors for susceptibility and severity of rheumatoid arthritis: A North‐east Indian population‐based study

Summary Rheumatoid arthritis ( RA ) is a complex, multifactorial, systemic autoimmune disease. Reports are suggestive of the role of HLA especially HLA ‐ DRB 1 alterations in RA pathogenesis. Existing data involving different geographical populations on the role of alterations in specific locus of HLA ‐ DRB 1 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 ‐ DRB 1 gene SNP s ( 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 ‐ DRB 1 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 SPSS v13.0 software. The HLA ‐ DRB 1 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 ‐ DRB 1 are associated with RA susceptibility. HLA ‐ DRB 1 rs13192471 SNP plays a critical role in RA susceptibility and severity in North‐east Indian cases and has prognostic significance in RA .