Associative role of HLA‐DRB1 SNP genotypes as risk factors for susceptibility and severity of rheumatoid arthritis: A North‐east Indian population‐based study

Abstract

Summary 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.

Association of Dietary Inflammatory Index (DII) with disease activity and inflammatory cytokines in the patients with rheumatoid arthritis

“…3 Multiple factors including genetic, female sex, exposure to tobacco smoke, obesity and changes in the microbiota are recognised to be involved in the development of RA. [4][5][6] Over the last few years, a growing body of evidence has shown the potential role of inflammation in the aetiology of RA. [7][8][9] The main feature of the disease is inflammation of the peripheral joints with systemic inflammation.…”

Genetics, Epigenetics, Cellular Immunology, and Gut Microbiota: Emerging Links With Graves’ Disease

“…Genetic factors also play an important role in other autoimmune diseases. HLA-DRB 1/rs13192471 confers a genetic predisposition to RA in a northeast Indian population ( Das et al, 2018 ). FoxP 3, VDR , PTPN 22, CTLA 4, and CD 40 gene polymorphisms were associated with susceptibility to autoimmune diseases including RA, systemic lupus erythematosus, alopecia areata, and psoriasis ( Wu et al, 2016 ; Bin Huraib et al, 2018 ; Hashemi et al, 2018 ; Moravvej et al, 2018 ; Fouad et al, 2019 ).…”

Optical Biosensors for the Detection of Rheumatoid Arthritis (RA) Biomarkers: A Comprehensive Review

“…Furthermore, research continues being carried out in order to find new biomarkers for rheumatoid arthritis, including proteins as 14-3-3 η [164], enzymes as secretory phospholipase A2 group IIA (sPLA2-IIA) [165], or polymorphisms as rs688136 from the vasoactive intestinal peptide (VIP) gene [166], or rs13192471 from the HLA-DRB1 gene [167].…”