Sheng Yu-jun, Xu Jian-hua, Wu Yong-gui, Zuo Xian-bo, Gao Jin-ping, Lin Yan, Zhu Zheng-wei, Wen Lei-lei, Yang Chao, Liu Lu, Cheng Yu-yan, Chang Yan, Yang Lu-lu, Zhou Fu-sheng, Tang Xian-fa, Zheng Xiao-dong, Yin Xian-yong, Tang Hua-yang, Sun Liang-dan, Cui Yong, Yang Sen, Zhang Xue-jun
Institute of Dermatology and Department of Dermatology, No.1 Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.
Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
Arthritis Res Ther. 2015 Mar 28;17(1):85. doi: 10.1186/s13075-015-0602-9.
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Currently, numerous genetic loci of SLE have been confirmed. Here we try to further explore additional genes contributing to SLE susceptibility in this study.
Forty nine single nucleotide polymorphisms (SNPs) with moderate-risk for SLE in previous study were genotyped in a large-scale replication study with a total of 3,522 cases and 8,252 controls using the Sequenom Massarray system. Association analyses were performed using logistic regression with gender or sample cohorts as a covariate through PLINK 1.07 software.
This replication effort confirmed five reported SLE susceptibility loci reaching genome-wide levels of significance (P(meta) <5.00 × 10(-08)): TNFSF4 (rs1418190, odds ratio (OR) = 0.81, P(meta) = 1.08 × 10(-08); rs4916219, OR = 0.80, P(meta )= 7.77 × 10(-09)), IRF8 (rs2934498, OR = 1.25, P(meta) = 4.97 × 10(-09)), miR-146a (rs2431697, OR = 0.69, P(meta) = 1.15 × 10(-22)), CD44 (rs2732547, OR = 0.82, P(meta) = 1.55 × 10(-11)), and TMEM39A (rs12494314, OR = 0.84, P(meta) = 1.01 × 10(-09)). Further logistic regression analysis indicated that the genetic effects within TNFSF4 detected in this study are independent from our previously reported signals.
This study increases the number of established susceptibility loci for SLE in Han Chinese population and highlights the contribution of multiple variants of modest effect. Although further studies will be required to identify the causal alleles within these loci, the findings make a significant step forward in our understanding of the genetic contribution to SLE in Chinese population.
系统性红斑狼疮（SLE）是一种多系统自身免疫性疾病。目前，众多SLE的基因位点已得到确认。在本研究中，我们试图进一步探索其他导致SLE易感性的基因。
使用Sequenom Massarray系统，对先前研究中具有中度SLE风险的49个单核苷酸多态性（SNP）在一项大规模重复研究中进行基因分型，该研究共有3522例病例和8252例对照。通过PLINK 1.07软件，以性别或样本队列作为协变量，使用逻辑回归进行关联分析。
这项重复研究确认了五个已报道的达到全基因组显著水平（P(meta)<5.00×10(-08)）的SLE易感基因座：TNFSF4（rs1418190，优势比（OR）=0.81，P(meta)=1.08×10(-08)；rs4916219，OR=0.80，P(meta)=7.77×10(-09)），IRF8（rs2934498，OR=1.25，P(meta)=4.97×10(-09)），miR-146a（rs2431697，OR=0.69，P(meta)=1.15×10(-22)），CD44（rs2732547，OR=0.82，P(meta)=1.55×10(-11)），以及TMEM39A（rs12494314，OR=0.84，P(meta)=1.01×10(-09)）。进一步的逻辑回归分析表明，本研究中在TNFSF4内检测到的遗传效应独立于我们先前报道的信号。
本研究增加了汉族人群中已确定的SLE易感基因座数量，并突出了多个中等效应变体的贡献。尽管需要进一步研究来确定这些基因座内的因果等位基因，但这些发现使我们对中国人群中SLE的遗传贡献的理解向前迈出了重要一步。
