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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
Author(s) -
Das S.,
Baruah C.,
Saikia A. K.,
Bose S.
Publication year - 2018
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.12347
Subject(s) - single nucleotide polymorphism , genotype , snp , rheumatoid arthritis , medicine , immunology , allele , rheumatology , human leukocyte antigen , heterozygote advantage , case control study , population , genetics , biology , antigen , gene , environmental health
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 .