Abstract
Background: This study aimed to assess the association of the angiopoietin-like protein 4 gene (ANGPTL4) variants and serum lipid levels, the risk of coronary artery disease (CAD) and ischemic stroke (IS), and response to atorvastatin therapy in a Southern Chinese Han population. Methods: Genotypes of the ANGPTL4 rs4076317, rs7255436, rs1044250 and rs2967605 in 1,654 unrelated subjects (CAD, 568; IS, 537; and controls, 549) were determined by the Snapshot technology. A total of 724 hyperlipidemic patients were treated with atorvastatin calcium tablet 20 mg/day for 8 weeks. Results: The rs2967605 CT/TT genotypes were associated with a decreased risk of CAD (adjusted OR=0.68, 95% CI=0.47-0.99, P=0.043 for CT/TT vs. CC) and IS (adjusted OR=0.55, 95% CI=0.38-0.80, P=0.020 for CT/TT vs. CC). Significant interactions were observed in gender, body mass index, alcohol consumption and diabetes. There were no significant effects of the four SNPs on angiographic severity of CAD. The subjects with the rs4076317 CG/CC genotypes in controls had higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels than the subjects with the GG genotype (P < 0.001). Functional predictions of the rs2967605 and rs4076317 were carried out using bioinformatics tools F-SNP. The results showed changes in the level of transcriptional regulation. The subjects with rs4076317CG/GG genotypes had lower TC and LDL-C levels than the subjects with CC genotype after atorvastatin treatment. Conclusions: The observed associations suggest that the ANGPTL4 variants have a potential role on serum lipid levels and atherosclerosis-related diseases in the Han population, especially ANGPTL4 rs4076317. Funding Statement: This study was supported by the Science Foundation of Guangxi Returned Oversea Scholars (No. 0991004) and the National Natural Science Foundation of China (No. 81460169). Declaration of Interests: All authors declare that they have no competing interest. Ethics Approval Statement: The study protocol was approved by the Ethics Committee of our First Affiliated Hospital (No. Lunshen 2009-Guike-018). Informed consent was obtained from all subjects.
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