该基因的遗传变异与缺血性中风易感性的关联研究。

Association study of genetic variants of the gene and susceptibility to ischemic stroke.

作者信息

Gong Qi, Ye Liping, Gui Huiwen, Liu Jing, Li Huanyin, Sun Qian

机构信息

Department of Neurology, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai 201199, People's Republic of China.

Nursing Department, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai 201199, People's Republic of China.

出版信息

Neuropsychiatr Dis Treat. 2019 Oct 24;15:3015-3020. doi: 10.2147/NDT.S215387. eCollection 2019.

DOI:10.2147/NDT.S215387

PMID:31749619

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6817949/

Abstract

BACKGROUND

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 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 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 rs6690733.

RESULTS

We found rs6690733 (C vs A: OR 1.34, 95% CI 1.13-1.59; =0.001) and rs12563308 (C vs T: OR 0.77, 95% CI 0.64-0.93, =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 <0.05). For rs6690733, the luciferase assay showed that promoter activity was significantly increased by 67% of plasmids containing the minor C allele compared with the major A allele in HEK293 cells.

CONCLUSION

Our study revealed genetic variants of the gene could contribute to susceptibility to IS through participating in the regulation of lipid metabolism.

摘要

背景

中风是全球导致寿命损失的第三大主要原因。血管生成素样蛋白3（ANGPTL3）在脂质代谢、动脉粥样硬化和中风发生中起重要作用。本研究的目的是评估该基因的遗传变异与缺血性中风（IS）风险的关联。

方法

进行了一项病例对照研究，以评估该基因的标签单核苷酸多态性（SNP）与IS风险以及血清脂质水平的关联。在HEK293T细胞系中进行双荧光素酶报告基因测定，以评估rs6690733的启动子活性。

结果

我们发现rs6690733（C与A：比值比1.34，95%置信区间1.13 - 1.59；P = 0.001）和rs12563308（C与T：比值比0.77，95%置信区间0.64 - 0.93，P = 0.007）与IS易感性显著相关。即使经过Bonferroni校正，这两个变异仍然显著（0.007×4 = 0.028）。SNP rs6690733的次要等位基因携带者的总胆固醇（TC）和低密度脂蛋白胆固醇（LDL - C）水平显著更高，而SNP rs12563308的次要等位基因携带者的TC和LDL - C水平显著更低（均P < 0.05）。对于rs6690733，荧光素酶测定显示，在HEK293细胞中，与主要A等位基因相比，含有次要C等位基因的质粒的启动子活性显著增加了67%。