Su Li, Chen Ziwen, Yan Yan, Liang Baoyun, Xie Juanjuan, Chen Qing, Tan Jinjing, Gu Lian
School of Public Health, Guangxi Medical University, Nanning, Guangxi, China.
First Affiliated Hospital, Guangxi University of Chinese Medicine, Nanning, Guangxi, China.
J Mol Neurosci. 2015 Nov;57(3):386-92. doi: 10.1007/s12031-015-0580-z. Epub 2015 May 22.
The tumor necrosis factor receptor-associated factor 6 (TRAF6) gene encodes a protein that acts downstream of the Toll-like receptor (TLR) pathway. TLRs activate inflammatory cascades and mediate inflammatory injury after cerebral ischemia. However, the role of TFAR6 gene polymorphisms in ischemic stroke (IS) remains unknown. This study aims to investigate the associations of TRAF6 gene polymorphisms with susceptibility to IS and IS-related quantitative traits in Southern Chinese Han population. A total of 816 IS cases and 816 age- and gender-matched controls were included. Two variants of the TRAF6 gene (rs5030411 and rs5030416) were genotyped using the Sequenom MassARRAY iPLEX platform. Our study showed that rs5030416 was significantly associated with increased susceptibility to IS in the additive model [ORadj 1.25(1.04-1.51), P adj = 0.019, P Bc = 0.038] and dominant model [ORadj 1.23(1.04-1.60), P adj = 0.021, P Bc = 0.042] after adjusting by age and sex and applying a Bonferroni correction. No significant association was found between rs5030411 and IS susceptibility (all P > 0.05). The haplotype rs5030416 (allele C)-rs5030411 (allele C) was significantly associated with IS susceptibility (P adj = 0.015). Moreover, a significant association of rs5030411 with TC levels in IS patients under the additive model [β 0.16(0.01-0.30), P adj = 0.034] and recessive model [β 0.45(0.12-0.78), P adj = 0.007] was observed after adjustment by age and sex. This association remained statistically significant under the recessive model (P Bc = 0.042) after Bonferroni correction. Our results suggest that TRAF6 gene polymorphisms may be involved in the pathogenesis of IS.
肿瘤坏死因子受体相关因子6（TRAF6）基因编码一种在Toll样受体（TLR）通路下游起作用的蛋白质。TLR激活炎症级联反应并介导脑缺血后的炎症损伤。然而，TRAF6基因多态性在缺血性卒中（IS）中的作用仍不清楚。本研究旨在探讨中国南方汉族人群中TRAF6基因多态性与IS易感性及IS相关数量性状的关联。共纳入816例IS患者和816例年龄及性别匹配的对照。使用Sequenom MassARRAY iPLEX平台对TRAF6基因的两个变体（rs5030411和rs5030416）进行基因分型。我们的研究表明，在年龄和性别校正并应用Bonferroni校正后，rs5030416在加性模型[ORadj 1.25（1.04 - 1.51），P adj = 0.019，P Bc = 0.038]和显性模型[ORadj 1.23（1.04 - 1.60），P adj = 0.021，P Bc = 0.042]中与IS易感性增加显著相关。未发现rs5030411与IS易感性之间存在显著关联（所有P>0.05）。单倍型rs5030416（等位基因C）-rs5030411（等位基因C）与IS易感性显著相关（P adj = 0.015）。此外，在年龄和性别校正后，观察到rs5030411在加性模型[β 0.16（0.01 - 0.30），P adj = 0.034]和隐性模型[β 0.45（0.12 - 0.78），P adj = 0.007]中与IS患者的总胆固醇（TC）水平显著相关。在Bonferroni校正后，该关联在隐性模型中仍具有统计学意义（P Bc = 0.042）。我们的结果表明，TRAF6基因多态性可能参与IS的发病机制。
