Association Between TRAF6 Gene Polymorphisms and Susceptibility of Ischemic Stroke in Southern Chinese Han Population

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.