The ACTB Variants and Alcohol Drinking Confer Joint Effect of Ischemic Stroke in Chinese Han Population

Aim: beta-actin (ACTB) participates in the vascular remodeling and contributes to the cardiovascular diseases. Herein, we investigated the associations of ACTB with hypertension and stroke. Methods: Three single-nucleotide polymorphisms in ACTB were selected for genotyping in 2,012 hypertension cases and 2,210 controls. The associations of ACTB with hypertension and stroke were examined in another follow-up study. Logistic and Cox regression were performed in a case-control study and a follow-up study, respectively. Additive scale interaction was examined by calculating the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (SI). The multiplicative interaction hazard ratio was calculated by fitting the Cox regression model. ACTB mRNA in peripheral blood mononuclear cells was measured in ischemic stroke (IS) cases and in controls. Results: The associations of rs852426 with hypertension and stroke had statistical significance in drinkers but not after Bonferroni correction. An additive interaction of rs852426 and drinking was observed for stroke incidence, the adjusted RERI was -0.907 (p=4.108 x 10(-4)), and the multiplicative interaction was still sound (HR=0.541, p=0.048). Furthermore, the significant interaction was further replicated in a nested case-control study. In the drinking population, the relative expression of ACTB mRNA in IS was lower (0.99 +/- 0.26) than that in controls (1.13 +/- 0.20), with a p value of 0.026. Conclusions: ACTB rs852426 was significantly associated with alcohol consumption on stroke risk, and the expression of ACTB mRNA in IS who had a drinking habit was significantly down-regulated. This finding will provide a novel insight into the prevention of stroke.