Multiple variants in 5q31.1 are associated with systemic lupus erythematosus susceptibility and sub-phenotypes in the Han Chinese population
Multiple variants in 5q31.1 are associated with systemic lupus erythematosus susceptibility and sub-phenotypes in the Han Chinese population
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5q31.1的多个变异与中国汉族人群系统性红斑狼疮易感性和亚表型相关
DOI：
10.1111/bjd.15362
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Cui Y
中科院分区：
文献类型：
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作者：
Wen L;Zhu Z;Yang C;Liu L;Zuo X;Morris DL;Dou J;Ye L;Cheng Y;Guo H;Huang H;Lin Y;Zhu C;Tang L;Chen M;Zhou Y;Ding Y;Liang B;Zhou F;Gao J;Tang X;Zheng X;Wang W;Yin X;Tang H;Sun L;Yang S;Zhang X;Sheng Y;Cui Y
背景一项先前的研究提供了多祖先队列中PPP2CA on 5q31.1与系统性红斑狼疮（SLE）之间遗传关联的证据，但在中国汉族人群中没有发现显著的关联证据。目的利用我们先前发表的全基因组关联研究（GWAS）的数据探讨该位点与SLE之间的关联。rs7726414和rs244689（在5q31.1中靠近TCF7和PPP2CA）被选为来自中国汉族人群（包括1047例病例和1205例对照）的大规模研究的候选独立关联。随后，3509例和8246对照基因型在两个进一步的复制研究。然后，我们调查了SNPs'协会与SLE亚表型和基因表达在外周血单核细胞。ResultsHighly显着协会与SLE在汉族人群中检测SNPs rs7726414和rs244689相结合的基因型数据，从我们以前的GWAS和两个独立的复制cohort。进一步的条件分析表明，这两个SNPs有助于独立的疾病易感性。发现rs7726414与SLE（诊断时年龄< 20岁）显著相关（P= 0.001）。SLE患者TCF7和PPP2CA信使RNA的表达水平与健康对照组相比显著降低。结论本研究首次在中国汉族人群中发现了5q31.1与SLE在全基因组水平显著相关的证据。这些发现表明，在5q31.1位点的变异不仅提供了新的见解SLE的遗传结构，但也有助于复杂的亚表型SLE。
BackgroundA previous study provided evidence for a genetic association betweenPPP2CAon 5q31.1 and systemic lupus erythematosus (SLE) across multi‐ancestral cohorts, but failed to find significant evidence for an association in the Han Chinese population.ObjectivesTo explore the association between this locus and SLE using data from our previously published genome‐wide association study (GWAS).MethodsSingle‐nucleotide polymorphisms (SNPs) rs7726414 and rs244689 (nearTCF7andPPP2CAin 5q31.1) were selected as candidate independent associations from a large‐scale study in a Han Chinese population consisting of 1047 cases and 1205 controls. Subsequently, 3509 cases and 8246 controls were genotyped in two further replication studies. We then investigated the SNPs' associations with SLE subphenotypes and gene expression in peripheral blood mononuclear cells.ResultsHighly significant associations with SLE in the Han Chinese population were detected for SNPs rs7726414 and rs244689 by combining the genotype data from our previous GWAS and two independent replication cohorts. Further conditional analyses indicated that these two SNPs contribute to disease susceptibility independently. A significant association with SLE, age at diagnosis < 20 years, was found for rs7726414 (P= 0·001). The expression levels ofTCF7andPPP2CAmessenger RNA in patients with SLE were significantly decreased compared with those in healthy controls.ConclusionsThis study found evidence for multiple associations with SLE in 5q31.1 at genome‐wide levels of significance for the first time in a Han Chinese population, in a combined genotype dataset. These findings suggest that variants in the 5q31.1 locus not only provide novel insights into the genetic architecture of SLE, but also contribute to the complex subphenotypes of SLE.