Das S, Baruah C, Saikia A K, Bose S
Department of Bio-engineering and Technology, Gauhati University, Guwahati, Assam, India.
Department of Medicine, Gauhati Medical College and Hospital, Guwahati, Assam, India.
Int J Immunogenet. 2018 Feb;45(1):1-7. doi: 10.1111/iji.12347. Epub 2017 Nov 23.
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.
类风湿关节炎（RA）是一种复杂的、多因素的全身性自身免疫性疾病。有报告提示HLA尤其是HLA - DRB1改变在RA发病机制中的作用。关于HLA - DRB1特定基因座改变在RA易感性和严重程度方面的作用，涉及不同地理人群的现有数据并不明确，印度东北部不同种族人群尚无相关数据，而该地区RA病例正惊人地增加。本研究旨在评估HLA - DRB1基因单核苷酸多态性（rs13192471、rs660895和rs6457617）与印度东北部不同种族人群RA易感性和严重程度的关联。在获得知情同意后，从临床特征明确的RA病例（符合美国风湿病学会1987年标准）（n = 123）和社区中年龄及性别匹配的健康对照（n = 156）采集全血。以病例和对照的基因组DNA为模板，使用扩增阻滞突变系统聚合酶链反应（ARMS - PCR）对所有RA和对照病例进行HLA - DRB1单核苷酸多态性分析。使用SPSSv13.0软件进行统计分析。HLA - DRB1 rs660895显示出野生型（AA）和杂合子（AG）基因型，但发现杂合子等位基因与RA风险降低相关，与对照组相比[比值比（OR）= 0.531，p = 0.024]。RA与对照病例之间rs6457617多态性分布的差异具有可比性[OR = 0.525，p = 0.079]。与对照组（46.75%）相比，RA病例中rs13192471变异基因型的分布显著更高（69.92%）（p < 0.001），与RA易感性增加相关[OR = 2.576，p < 0.001]，与对照组相比，也与RA病例病情进展至严重程度相关[OR = 2.404，p = 0.048]。组合分析中，rs13192471变异基因型的存在也与RA易感性增加相关[OR = 8.267，p = 0.026]和RA严重程度相关[OR = 3.647，p = 0.280]。HLA - DRB1改变与RA易感性相关。HLA - DRB1 rs13192471单核苷酸多态性在印度东北部病例的RA易感性和严重程度中起关键作用，对RA具有预后意义。
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