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DNAH11 rs12670798 variant and G × E interactions on serum lipid levels, coronary heart disease, ischemic stroke and the lipid-lowering efficacy of atorvastatin.

ABSTRACT: Previous genome-wide association studies have showed that the rs12670798 variant in the dynein axonemal heavy chain 11 gene (DNAH11) is associated with some serum lipid phenotypes. The present study was undertaken to detect the DNAH11 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 DNAH11 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 (P = 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, P = 0.071; CC genotype: OR = 1.590, 95% CI = 1.109-2.278, P = 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, P = 0.005; CC genotype: OR = 1.722, 95% CI = 1.192-2.488, P = 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 DNAH11 rs12670798 may interact with the gender, age, body mass index, cigarette smoking, and alcohol consumption to affect the risk of CHD and IS. The DNAH11 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.

SUBMITTER: Shen SW

PROVIDER: S-EPMC6965851 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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DNAH11 rs12670798 variant and G × E interactions on serum lipid levels, coronary heart disease, ischemic stroke and the lipid-lowering efficacy of atorvastatin.

Shen Shao-Wen SW Yin Rui-Xing RX Huang Feng F Wu Jin-Zhen JZ Cao Xiao-Li XL Chen Wu-Xian WX

International journal of clinical and experimental pathology 20171101 11

Previous genome-wide association studies have showed that the rs12670798 variant in the dynein axonemal heavy chain 11 gene (DNAH11) is associated with some serum lipid phenotypes. The present study was undertaken to detect the DNAH11 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 ...[more]

PMID: 31966465

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Project description:Zhibitai, a natural lipid-lowering Chinese medicine, is well tolerated in patients and has low incidence of adverse events. In this study, we evaluated the efficacy, safety, and side effects of Zhibitai in combination with low dose Atorvastatin compared to high dose Atorvastatin in patients with coronary heart disease or at high risk of coronary heart disease.This was a randomized, double-blind, multi-center clinical trial on 720 patients with coronary heart disease or at high risk of coronary heart disease. The patients were randomly assigned to a Zhibitai-Atorvastatin group (480 mg Zhibitai twice daily plus 10 mg atorvastatin once daily) or Monotherapy group (40 mg Atorvastatin once daily). Blood samples were obtained at baseline, week 4, and week 8 after a minimum 8-hour fast. Efficacy was evaluated in terms of the changes in the following parameters: lipoprotein profiles [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)]. Safety was assessed throughout the study by clinical laboratory tests including liver function [alanine transaminase, aspartate transaminase] and renal function [blood urea nitrogen], and creatine kinase; physical examination; and adverse events monitoring.TC, TG, LDL-C levels were significantly decreased andHDL-C levels were significantly increased at week 4 and week 8 (all P < 0.05) in both groups but had no significant differences between the two groups (P > 0.05). In subgroup analyses, Zhibitai-Atorvastatin Group produced significantly greater reduction in TG compared with Monotherapy Group at week 8 in patients with TG > 203.72mg/dL (P < 0.01). Among patients with LDL-C levels > 131.48 mg/dL, Zhibitai-Atorvastatin Group produced a greater reduction of LDL-C levels compared with the Monotherapy Group at week 4 (P < 0.05). The incidence of liver dysfunction, headache, or gastrointestinal intolerance was significantly lower in the Zhibitai-Atorvastatin Group compared with Monotherapy Group during the 8-week study peroid (P < 0.001). There were no significant differences in renal function, myopathy, and other adverse events between the groups.Overall the two groups have similar lipid regulation efficacy. Zhibitai plus low dose Atorvastatin is more efficacious in lowering TG in patients with TG > 203.72 mg/dL at week 8. There are fewer side effects in Zhibitai plus low dose Atorvastatin group. Long term follow up is required to evaluate cardiovascular outcomes.

Dataset Information

DNAH11 rs12670798 variant and G × E interactions on serum lipid levels, coronary heart disease, ischemic stroke and the lipid-lowering efficacy of atorvastatin.

Publications

<i>DNAH11</i> rs12670798 variant and G × E interactions on serum lipid levels, coronary heart disease, ischemic stroke and the lipid-lowering efficacy of atorvastatin.

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