Abstract
BackgroundThis study aimed to assess the association between the angiopoietin-like protein 4 gene (ANGPTL4) single nucleotide polymorphisms (SNPs) 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.MethodsGenotypes of the ANGPTL4 rs4076317, rs7255436, rs1044250 and rs2967605 SNPs in 1,654 unrelated subjects (CAD, 568; IS, 537; and controls, 549) were determined by the Snapshot technology. Another group of 724 hyperlipidemic patients was selected and treated with atorvastatin calcium tablet 20 mg/day for 8 weeks.ResultsThe 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). There was no significant association between the four SNPs and 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; a P < 0.0018 was regarded statistically significant by the Bonferroni correction). The subjects with rs4076317CG/GG genotypes had lower TC and LDL-C levels than the subjects with CC genotype after atorvastatin treatment (P < 0.001).ConclusionsThe observed associations suggest that the ANGPTL4 variants have a potential role on serum lipid levels and atherosclerosis-related diseases in the Chinese Han population, especially the ANGPTL4 rs4076317 and rs2967605 SNPs.
Highlights
This study aimed to assess the association between the angiopoietin-like protein 4 gene (ANGPTL4) single nucleotide polymorphisms (SNPs) 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
The rs2967605T allele carriers had lower risk of CAD and IS
We showed that the ANGPTL4 rs4076317 SNP changed the effects of atorvastatin on serum lipid levels
Summary
This study aimed to assess the association between the angiopoietin-like protein 4 gene (ANGPTL4) single nucleotide polymorphisms (SNPs) 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. The retention of serum lipoproteins in the artery wall is a key initiator of atherosclerosis [6]. Angiopoietin-like protein 4 gene (ANGPTL4) is one of the novel genes associated with serum lipid levels in the Caucasian population [7, 8]. Previous functional studies revealed that ANGPTL4 regulated plasma triglyceride (TG) levels by inhibiting lipoprotein lipase (LPL) [13,14,15,16]. ANGPTL4-deficient mice decreased serum TG levels by increasing LPL activity. The ANGPTL4 transgenic mice elevated serum TG and reduced LPL activity [14, 15, 19,20,21]
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