Gupta V, Kumar S, Pratap A, Singh R, Kumari R, Kumar S, Aggarwal A, Misra R
1 Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
2 Department of Biochemistry, King George's Medical University, Lucknow, India.
Lupus. 2018 Oct;27(12):1973-1979. doi: 10.1177/0961203318786432. Epub 2018 Jul 24.
Several susceptibility genes have been associated with systemic lupus erythematosus (SLE) across different populations worldwide. However, data on association between genetic polymorphisms and SLE from Indian population is scarce. We aimed to replicate the association of single nucleotide polymorphisms (SNPs) in ITGAM, TNFSF4, TNFAIP3 and STAT4 genes with susceptibility to SLE in a North Indian population. Three hundred and ninety-four SLE patients and 583 unrelated healthy controls of the same ethnic background were enrolled. All samples were genotyped for SNPs in ITGAM (rs1143679), TNFSF4 (rs2205960), TNFAIP3 (rs5029939) and STAT4 (rs7574865) using TaqMan genotyping assay. At allele level, significant association with susceptibility to SLE was detected with polymorphisms in ITGAM (A vs. G, odds ratio (OR) = 1.73, 95% confidence interval (CI) = 1.30-2.30, p < 0.001), TNFSF4 (T vs. G, OR = 1.33, 95% CI = 1.08-1.64, p < 0.01), TNFAIP3 (G vs. C, OR = 1.91, 95% CI = 1.27-2.85, p < 0.01) and STAT4 (T vs. G, OR = 1.38, 95% CI = 1.13-1.69, p < 0.01). All four SNPs were associated with SLE under a dominant model with an OR of 1.47 (95% CI = 1.07-2.04, p < 0.05) for ITGAM, 1.30 (95% CI = 1.01-1.69, p < 0.05) for TNFSF4, 1.90 (95% CI = 1.25-2.90, p < 0.01) for TNFAIP3 and 1.38 (95% CI = 1.06-1.78, p < 0.05) for STAT4. Under a recessive model, significant association was found with ITGAM (OR = 4.87, 95% CI = 2.17-10.91, p < 0.001), TNFSF4 (OR = 1.84, 95% CI = 1.13-3.00, p < 0.05) and STAT4 (OR = 1.82, 95% CI = 1.19-2.77, p < 0.01). In conclusion, single nucleotide polymorphisms in ITGAM, TNFSF4, TNFAIP3 and STAT4 genes are associated with susceptibility to SLE in a North Indian population.
在全球不同人群中，已有多个易感基因与系统性红斑狼疮（SLE）相关联。然而，来自印度人群的关于基因多态性与SLE之间关联的数据却很匮乏。我们旨在在北印度人群中重复验证整合素α-M（ITGAM）、肿瘤坏死因子超家族成员4（TNFSF4）、肿瘤坏死因子α诱导蛋白3（TNFAIP3）和信号转导子和转录激活子4（STAT4）基因中的单核苷酸多态性（SNP）与SLE易感性之间的关联。招募了394例SLE患者和583例具有相同种族背景的无关健康对照。使用TaqMan基因分型检测法对所有样本进行ITGAM（rs1143679）、TNFSF4（rs2205960）、TNFAIP3（rs5029939）和STAT4（rs7574865）基因SNP的基因分型。在等位基因水平上，检测到ITGAM基因多态性（A与G相比，优势比（OR）=1.73，95%置信区间（CI）=1.30 - 2.30，p<0.001）、TNFSF4基因多态性（T与G相比，OR = 1.33，95% CI = 1.08 - 1.64，p<0.01）、TNFAIP3基因多态性（G与C相比，OR = 1.91，95% CI = 1.27 - 2.85，p<0.01）和STAT4基因多态性（T与G相比，OR = 1.38，95% CI = 1.13 - 1.69，p<0.01）与SLE易感性显著相关。在显性模型下，所有四个SNP均与SLE相关，ITGAM的OR为1.47（95% CI = 1.07 - 2.04，p<0.05），TNFSF4的OR为1.30（95% CI = 1.01 - 1.69，p<0.05），TNFAIP3的OR为1.90（95% CI = 1.25 - 2.90，p<0.01），STAT4的OR为1.38（95% CI = 1.06 - 1.78，p<0.05）。在隐性模型下，发现ITGAM（OR = 4.87，95% CI = 2.17 - 10.91，p<0.001）、TNFSF4（OR = 1.84，95% CI = 1.13 - 3.00，p<0.05）和STAT4（OR = 1.82，95% CI = 1.19 - 2.77，p<0.01）存在显著关联。总之，ITGAM、TNFSF4、TNFAIP3和STAT4基因中的单核苷酸多态性与北印度人群的SLE易感性相关。
