DataSheet_2_Exploration of the association between the single-nucleotide polymorphism of co-stimulatory system and rheumatoid arthritis.docx

IntroductionThe human leukocyte antigen (HLA) has been linked to the majority of autoimmune diseases (ADs). However, non-HLA genes may be risk factors for ADs. A number of genes encoding proteins involved in regulating T-cell and B-cell function have been identified as rheumatoid arthritis (RA) susceptibility genes.
MethodsIn this study, we investigated the association between RA and single-nucleotide polymorphisms (SNPs) of co-stimulatory or co-inhibitory molecules in 124 RA cases and 100 healthy controls without immune-related diseases [including tumor necrosis factor superfamily member 4 (TNFSF4), CD28, cytotoxic T-lymphocyte–associated protein 4 (CTLA4), and programmed cell death protein 1 (PDCD1)].
ResultsThe results showed that there were 13 SNPs associated with RA, including rs181758110 of TNFSF4 (CC vs. CT, p = 0.038); rs3181096 of CD28 (TT vs. CC + CT, p = 0.035; CC vs. TT, p = 0.047); rs11571315 (TT vs. CT, p = 0.045), rs733618 (CC vs. TT + CT, p = 0.043), rs4553808 (AA vs. AG vs. GG, p = 0.035), rs11571316 (GG vs. AG vs. AA, p = 0.048; GG vs. AG + AA, p = 0.026; GG vs. AG, p = 0.014), rs16840252 (CC vs. CT vs. TT, p = 0.007; CC vs. CT, p = 0.011), rs5742909 (CC vs. CT vs. TT, p = 0.040), and rs11571319 of CTLA4 (GG vs. AG vs. AA, p < 0.001; GG vs. AG + AA, p = 0.048; AA vs. GG + AG, p = 0.001; GG vs. AA, p = 0.008; GG vs. AG, p ≤ 0.001); and rs10204525 (TT vs. CT + CC, p = 0.024; TT vs. CT, p = 0.021), rs2227982 (AA vs. GG, p = 0.047), rs36084323 (TT vs. CT vs. CC, p = 0.022; TT vs. CT + CC, p = 0.013; CC vs. TT + CT, p = 0.048; TT vs. CC, p = 0.008), and rs5839828 of PDCD1 (DEL vs. DEL/G vs. GG, p = 0.014; DEL vs. DEL/G + GG, p = 0.014; GG vs. DEL + DEL/G, p = 0.025; DEL vs. GG, p = 0.007).
DiscussionConsequently, these SNPs may play an important role in immune regulation, and further research into the role of these SNPs of immune regulatory genes in the pathogenesis of RA is required.

引言 人类白细胞抗原（HLA）与绝大多数自身免疫性疾病（ADs）密切相关。然而，非HLA基因亦可作为自身免疫性疾病的风险因素。目前已有多个编码参与调控T细胞、B细胞功能的蛋白的基因被鉴定为类风湿关节炎（RA）易感基因。
方法 本研究纳入124例类风湿关节炎患者与100名无免疫相关疾病的健康对照者，旨在探究共刺激或共抑制分子的单核苷酸多态性（SNPs）与类风湿关节炎的关联。本次检测的分子包括肿瘤坏死因子超家族成员4（TNFSF4）、CD28、细胞毒性T淋巴细胞相关蛋白4（CTLA4）以及程序性细胞死亡蛋白1（PDCD1）。
结果 本研究结果显示，共13个单核苷酸多态性位点与类风湿关节炎存在显著关联：包括TNFSF4的rs181758110（CC基因型与CT基因型比较，p=0.038）；CD28的rs3181096（TT基因型与CC+CT基因型比较，p=0.035；CC基因型与TT基因型比较，p=0.047）；CTLA4的rs11571315（TT基因型与CT基因型比较，p=0.045）、rs733618（CC基因型与TT+CT基因型比较，p=0.043）、rs4553808（AA、AG与GG基因型比较，p=0.035）、rs11571316（GG、AG与AA基因型比较，p=0.048；GG基因型与AG+AA基因型比较，p=0.026；GG基因型与AG基因型比较，p=0.014）、rs16840252（CC、CT与TT基因型比较，p=0.007；CC基因型与CT基因型比较，p=0.011）、rs5742909（CC、CT与TT基因型比较，p=0.040）以及rs11571319（GG、AG与AA基因型比较，p<0.001；GG基因型与AG+AA基因型比较，p=0.048；AA基因型与GG+AG基因型比较，p=0.001；GG基因型与AA基因型比较，p=0.008；GG基因型与AG基因型比较，p≤0.001）；以及PDCD1的rs10204525（TT基因型与CT+CC基因型比较，p=0.024；TT基因型与CT基因型比较，p=0.021）、rs2227982（AA基因型与GG基因型比较，p=0.047）、rs36084323（TT、CT与CC基因型比较，p=0.022；TT基因型与CT+CC基因型比较，p=0.013；CC基因型与TT+CT基因型比较，p=0.048；TT基因型与CC基因型比较，p=0.008）以及rs5839828（缺失型（DEL）、DEL/G与GG基因型比较，p=0.014；缺失型与DEL/G+GG基因型比较，p=0.014；GG基因型与DEL+DEL/G基因型比较，p=0.025；缺失型与GG基因型比较，p=0.007）。
讨论 综上，上述单核苷酸多态性位点可能在免疫调控过程中发挥重要作用，后续仍需进一步研究免疫调控基因的这些多态性位点在类风湿关节炎发病机制中的具体功能。