Qi Gong,1,* Liping Ye,2,* Huiwen Gui,1 Jing Liu,1 Huanyin Li,1 Qian Sun1 1Department of Neurology, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai 201199, People’s Republic of China; 2Nursing Department, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai 201199, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huanyin LiDepartment of Neurology, Minhang Branch, Zhongshan Hospital, Fudan University, 170 Shenlong Road, Minhang District, Shanghai 201199, People’s Republic of ChinaTel/Fax +86 216 492 3400Email li_huanyin@sina.comBackground: Stroke ranks as the third-leading cause of years of life lost worldwide. ANGPTL3 plays important roles in lipid metabolism, atherosclerosis, and occurrence of stroke. The purpose of this study was to evaluate associations of genetic variants in the ANGPTL3 gene with ischemic stroke (IS) risk.Methods: A case–control study was conducted to evaluate the associations of tag single-nucleotide polymorphisms (SNPs) of the ANGPTL3 gene and risk of IS, as well as serum lipid levels. Dual-luciferase reporter assays in the HEK293T cell line was conducted to evaluate the promoter activity of ANGPTL3 rs6690733.Results: We found rs6690733 (C vs A: OR 1.34, 95% CI 1.13–1.59; P=0.001) and rs12563308 (C vs T: OR 0.77, 95% CI 0.64–0.93, P=0.007) were significantly associated with susceptibility to IS. Even corrected for Bonferroni adjustment, the two variants were still significant (0.007×4=0.028). Carriers of the minor allele of SNP rs6690733 had significantly higher levels of TC and LDL-C, while carriers of the minor allele of SNP rs12563308 had significantly lower levels of TC and LDL-C (all P