Variants in TNFSF4, TNFAIP3, TNIP1, BLK, SLC15A4 and UBE2L3 interact to confer risk of systemic lupus erythematosus in Chinese population
Variants in TNFSF4, TNFAIP3, TNIP1, BLK, SLC15A4 and UBE2L3 interact to confer risk of systemic lupus erythematosus in Chinese population
复制标题
DOI：
10.1007/s00296-013-2864-3
复制
发表时间：
2013
影响因子：
4
通讯作者：
X. Zuo;Y. Sheng;Su-juan Hu;Jinping Gao;Yang Li;Huayang Tang;Xianfa Tang;Hui Cheng;X. Yin;L. Wen;Liangdan Sun;Sen Yang;Yong Cui;Xuejun Zhang
中科院分区：
文献类型：
--
作者：
X. Zuo;Y. Sheng;Su-juan Hu;Jinping Gao;Yang Li;Huayang Tang;Xianfa Tang;Hui Cheng;X. Yin;L. Wen;Liangdan Sun;Sen Yang;Yong Cui;Xuejun Zhang
本研究通过对NF-κB信号通路的全基因组关联研究，发现了TNF-κ F 4、TNFAIP 3、TNIP 1、BLK、SLC 15 A4和UBE 2 L3等与SLE相关的基因。在这项研究中，我们探索了这六个基因的关联模式，并寻找可能的基因-基因相互作用的基础上确定的单核苷酸多态性（SNPs），通过使用逻辑回归分析在4,199例和8,255名对照的组合样本。在隐性模型下，所有这些SNP的关联性最显著。此外，在本研究中观察到这些SNP之间的显著相互作用：TNFSF 4和TNIP 1 SNP（P调整= 1.68E-10），TNFSF 4和SLC 15 A4 SNP（P调整= 3.55E-08），TNFSF 4和UBE 2L 3 SNP（P调整= 8.74E-13），TNIP 1和BLK SNP（P调整= 9.45E-10），TNIP 1和UBE 2L 3 SNP TNFAIP 3和UBE 2L 3 SNP（P调整= 3.06E-14）以及BLK和SLC 15 A4 SNP（P调整= 4.51E-12）。这些结果可能有助于我们了解SLE遗传相互作用，并解释某些患者发生SLE的额外风险。
Our previous genome-wide association studies on SLE have identified several susceptibility genes involved in NF-κB signaling pathway, includingTNFSF4,TNFAIP3,TNIP1,BLK,SLC15A4andUBE2L3.The aim of this study is to investigate the association model (additive, dominant, recessive) of these genes and search for possible gene–gene interactions between them. In this study, we explored the association model of these six genes and search for possible gene–gene interactions based on identified single-nucleotide polymorphisms (SNPs) among them by using logistic regression analysis in the combined sample of 4,199 cases and 8,255 controls. The most significant association evidence was observed under recessive model for all of these SNPs. Besides, significant interactions between these SNPs were observed in this study: the TNFSF4 and TNIP1 SNPs (Padjusted= 1.68E−10), the TNFSF4 and SLC15A4 SNPs (Padjusted= 3.55E−08), the TNFSF4 and UBE2L3 SNPs (Padjusted= 8.74E−13), the TNIP1 and BLK SNPs (Padjusted= 9.45E−10), the TNIP1 and UBE2L3 SNPs (Padjusted= 8.25E−11), the TNFAIP3 and UBE2L3 SNPs (Padjusted= 3.06E−14) and the BLK and SLC15A4 SNPs (Padjusted= 4.51E−12). These results may contribute to our understanding of SLE genetic interactions and account for the additional risk of certain patients to develop SLE.