Shen Shao-Wen, Yin Rui-Xing, Huang Feng, Wu Jin-Zhen, Cao Xiao-Li, Chen Wu-Xian
Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University Nanning, Guangxi, China.
Department of Neurology, The First Affiliated Hospital, Guangxi Medical University Nanning, Guangxi, China.
Int J Clin Exp Pathol. 2017 Nov 1;10(11):11147-11158. eCollection 2017.
Previous genome-wide association studies have showed that the rs12670798 variant in the dynein axonemal heavy chain 11 gene () is associated with some serum lipid phenotypes. The present study was undertaken to detect the rs12670798 variant and G × E interactions on serum lipid levels, coronary heart disease (CHD), ischemic stroke (IS), and the lipid-lowering efficacy of atorvastatin in the Chinese Han population. This study included 1,108 unrelated patients (CHD, 568 and IS, 540) and 541 healthy controls. Genotypes of the rs12670798 were determined by the Snapshot technology. A total of 724 hyperlipidemic patients were treated with atorvastatin calcium tablet 20 mg per day for 8 weeks after genotyping. Serum total cholesterol (TC) levels in controls were different among the three genotypes of the rs12670798 ( = 0.019), the C allele carriers had higher TC levels than the C allele non-carriers. The C allele carriers were associated with an increased risk of CHD (CT genotype: OR = 1.345, 95% CI = 0.975-1.855, = 0.071; CC genotype: OR = 1.590, 95% CI = 1.109-2.278, = 0.012). The C allele carriers were also associated with an increased risk of IS (CT genotype: OR = 1.597, 95% CI = 1.153-2.213, = 0.005; CC genotype: OR = 1.722, 95% CI = 1.192-2.488, = 0.004). The C allele carriers had lower TC, low-density lipoprotein cholesterol, apolipoprotein (Apo) A1 and ApoB levels than the C allele non-carriers after atorvastatin treatment. Stratified analysis showed that the rs12670798 may interact with the gender, age, body mass index, cigarette smoking, and alcohol consumption to affect the risk of CHD and IS. The rs12670798 variant was associated with elevated serum TC levels, and increased risk of CHD and IS in the Chinese Han population. The C allele carriers had higher serum TC levels and the risk of CHD and IS than the C allele non-carriers, but they had lower TC, LDL-C, ApoA1 and ApoB levels than the C allele non-carriers after atorvastatin treatment.
以往全基因组关联研究表明，动力蛋白轴丝重链11基因（）中的rs12670798变异与某些血脂表型相关。本研究旨在检测rs12670798变异以及基因与环境（G×E）相互作用对中国汉族人群血脂水平、冠心病（CHD）、缺血性脑卒中（IS）和阿托伐他汀降脂疗效的影响。本研究纳入了1108例无亲缘关系的患者（冠心病患者568例，缺血性脑卒中患者540例）和541例健康对照者。采用Snapshot技术测定rs12670798的基因型。共有724例高脂血症患者在基因分型后接受每日20mg阿托伐他汀钙片治疗8周。rs12670798的三种基因型在对照组中的血清总胆固醇（TC）水平存在差异（=0.019），C等位基因携带者的TC水平高于非C等位基因携带者。C等位基因携带者患冠心病的风险增加（CT基因型：OR=1.345，95%CI=0.975-1.855，=0.071；CC基因型：OR=1.590，95%CI=1.109-2.278，=0.012）。C等位基因携带者患缺血性脑卒中的风险也增加（CT基因型：OR=1.597，95%CI=1.153-2.213，=0.005；CC基因型：OR=1.722，95%CI=1.192-2.488，=0.004）。阿托伐他汀治疗后，C等位基因携带者的TC、低密度脂蛋白胆固醇、载脂蛋白（Apo）A1和ApoB水平低于非C等位基因携带者。分层分析表明，rs12670798可能与性别、年龄、体重指数、吸烟和饮酒相互作用，影响冠心病和缺血性脑卒中的发病风险。rsl2670798变异与中国汉族人群血清TC水平升高以及冠心病和缺血性脑卒中发病风险增加相关。C等位基因携带者的血清TC水平以及冠心病和缺血性脑卒中的发病风险高于非C等位基因携带者，但阿托伐他汀治疗后，他们的TC、低密度脂蛋白胆固醇、载脂蛋白A1和载脂蛋白B水平低于非C等位基因携带者。
