Zuo Xian-Bo, Sheng Yu-Jun, Hu Su-Juan, Gao Jin-Ping, Li Yang, Tang Hua-Yang, Tang Xian-Fa, Cheng Hui, Yin Xian-Yong, Wen Lei-Lei, Sun Liang-Dan, Yang Sen, Cui Yong, Zhang Xue-Jun
Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, Hefei, Anhui, China.
Rheumatol Int. 2014 Apr;34(4):459-64. doi: 10.1007/s00296-013-2864-3. Epub 2013 Oct 4.
Our previous genome-wide association studies on SLE have identified several susceptibility genes involved in NF-κB signaling pathway, including TNFSF4, TNFAIP3, TNIP1, BLK, SLC15A4 and UBE2L3. 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 (P adjusted = 1.68E-10), the TNFSF4 and SLC15A4 SNPs (P adjusted = 3.55E-08), the TNFSF4 and UBE2L3 SNPs (P adjusted = 8.74E-13), the TNIP1 and BLK SNPs (P adjusted = 9.45E-10), the TNIP1 and UBE2L3 SNPs (P adjusted = 8.25E-11), the TNFAIP3 and UBE2L3 SNPs (P adjusted = 3.06E-14) and the BLK and SLC15A4 SNPs (P adjusted = 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.
我们之前针对系统性红斑狼疮（SLE）开展的全基因组关联研究已经确定了几个参与核因子κB（NF-κB）信号通路的易感基因，包括肿瘤坏死因子配体超家族成员4（TNFSF4）、肿瘤坏死因子α诱导蛋白3（TNFAIP3）、TNFAIP3相互作用蛋白1（TNIP1）、B淋巴细胞酪氨酸激酶（BLK）、溶质载体家族15成员4（SLC15A4）和泛素结合酶E2L3（UBE2L3）。本研究的目的是探究这些基因的关联模式（加性、显性、隐性），并寻找它们之间可能存在的基因-基因相互作用。在本研究中，我们在4199例病例和8255例对照的合并样本中，通过逻辑回归分析，基于已确定的单核苷酸多态性（SNP）探究了这六个基因的关联模式，并寻找它们之间可能存在的基因-基因相互作用。所有这些SNP在隐性模型下观察到最显著的关联证据。此外，本研究还观察到这些SNP之间存在显著的相互作用：TNFSF4和TNIP1的SNP（校正P值 = 1.68×10⁻¹⁰）、TNFSF4和SLC15A4的SNP（校正P值 = 3.55×10⁻⁸）、TNFSF4和UBE2L3的SNP（校正P值 = 8.74×10⁻¹³）、TNIP1和BLK的SNP（校正P值 = 9.45×10⁻¹⁰）、TNIP1和UBE2L3的SNP（校正P值 = 8.25×10⁻¹¹）、TNFAIP3和UBE2L3的SNP（校正P值 = 为3.06×10⁻¹⁴）以及BLK和SLC15A4的SNP（校正P值 = 4.51×10⁻¹²）。这些结果可能有助于我们理解SLE的基因相互作用，并解释某些患者发生SLE的额外风险。
