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ANGPTL3 variants and risk of ischaemic stroke

Variants of the ANGPTL3 gene, encoding angiopoietin-like 3 protein, can contribute to susceptibility to ischaemic stroke in the Chinese population via effects on the regulation of lipid metabolism. This case-control study included 989 cases of ischaemic stroke (54% aged ≥60 years, 63% male, 45% with hypercholesterolaemia), confirmed by clinical history and neurological examination, and 990 matched controls. Single-nucleotide polymorphisms (SNPs) within the ANGPTL3 gene were selected using criteria of minor-allele frequency >5% in the Chinese Han population, with linkage disequilibrium r2 values <0.8 for candidate SNPs. Four candidate SNPs (rs12048208, rs6690733, rs12563308, and rs72641123) were included. Logistic regression analysis was used to calculated odds ratios and 95% confidence intervals (CI) for the association between polymorphisms of the ANGPTL3 gene and risk of ischaemic stroke, adjusted for age, sex, smoking and drinking status, body-mass index, hypertension, diabetes, and hypercholesterolaemia. The study showed that two ANGPTL3 SNPs - rs6690733 (C vs A alleles: odds ratio 1.34, 95% CI 1.13–1.59; p=0.001) and rs12563308 (C vs T alleles: odds ratio 0.77, 95% CI 0.64–0.93, P=0.007) were significantly associated with susceptibility to ischaemic stroke. Carriers of the minor allele of SNP rs6690733 also had higher levels of total and low-density lipoprotein cholesterol, whereas carriers of the rs12563308 SNP had lower levels of both parameters, when compared with controls. These findings add support for ANGPTL3 as a novel therapeutic target in to reduce the residual risk of cardiovascular events.
Association study of genetic variants of the ANGPTL3 gene and susceptibility to ischemic stroke.

Gong Q, Ye L, Gui H et al.