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ACTB 变异与饮酒在中国汉族人群中共同作用导致缺血性脑卒中。

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

机构信息

Department of Cardiology, Affiliated Yixing People's Hospital of Jiangsu University, People's Hospital of Yixing City.

Department of Neurology, Affiliated Yixing People's Hospital of Jiangsu University, People's Hospital of Yixing City.

出版信息

J Atheroscler Thromb. 2020 Mar 1;27(3):226-244. doi: 10.5551/jat.49536. Epub 2019 Jul 19.

DOI:10.5551/jat.49536
PMID:31327802
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7113141/
Abstract

AIM

β-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=4.108×10), 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.

摘要

目的

β-肌动蛋白(ACTB)参与血管重塑,导致心血管疾病。本研究旨在探讨 ACTB 与高血压和中风的关系。

方法

在 2012 例高血压病例和 2210 例对照中,选择 ACTB 中的三个单核苷酸多态性进行基因分型。在另一项随访研究中,检查了 ACTB 与高血压和中风的关系。病例对照研究中采用逻辑回归,随访研究中采用 Cox 回归。通过计算交互归因超额危险度(RERI)、交互归因比例(AP)和协同指数(SI)来检验加性尺度交互作用。通过拟合 Cox 回归模型计算乘法交互作用危害比。在缺血性中风(IS)病例和对照组中测量外周血单核细胞中的 ACTB mRNA。

结果

rs852426 与高血压和中风的关联在饮酒者中有统计学意义,但在经过 Bonferroni 校正后无统计学意义。rs852426 与饮酒之间存在中风发病的相加交互作用,调整后的 RERI 为-0.907(p=4.108×10),乘法交互作用仍然存在(HR=0.541,p=0.048)。此外,在嵌套病例对照研究中也验证了这种显著的交互作用。在饮酒人群中,IS 患者的 ACTB mRNA 相对表达水平较低(0.99±0.26),明显低于对照组(1.13±0.20),p 值为 0.026。

结论

ACTB rs852426 与中风风险与饮酒显著相关,且有饮酒习惯的 IS 患者中 ACTB mRNA 的表达明显下调。这一发现为中风的预防提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e074/7113141/3a9dc6ff8eb2/jat-27-226-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e074/7113141/09ac868224e4/jat-27-226-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e074/7113141/1c91f3b1676f/jat-27-226-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e074/7113141/e43ecca2167d/jat-27-226-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e074/7113141/3a9dc6ff8eb2/jat-27-226-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e074/7113141/09ac868224e4/jat-27-226-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e074/7113141/1c91f3b1676f/jat-27-226-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e074/7113141/e43ecca2167d/jat-27-226-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e074/7113141/3a9dc6ff8eb2/jat-27-226-g004.jpg

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