ZPR1 基因型可预测家族性高胆固醇血症患者的心肌梗死。
The ZPR1 genotype predicts myocardial infarction in patients with familial hypercholesterolemia.
机构信息
Genetic Dyslipidemias Clinic of the Montreal Clinical Research Institute, Québec, Canada.
Genetic Dyslipidemias Clinic of the Montreal Clinical Research Institute, Québec, Canada; Division of Endocrinology, Department of Medicine, Université de Montreal, Québec, Canada.
出版信息
J Clin Lipidol. 2020 Sep-Oct;14(5):660-666. doi: 10.1016/j.jacl.2020.07.008. Epub 2020 Jul 24.
BACKGROUND
The rs964184 variant in the ZPR1 gene has been associated with blood lipids and cardiovascular disease risk in the general population through genome-wide association study, but its effect in patients with familial hypercholesterolemia (FH) has never been studied.
OBJECTIVE
The objectives of the present study are to investigate the effect of the rs964184 SNP on blood lipids and on the risk of incident myocardial infarction (MI) in patients with FH.
METHODS
This study included 725 patients with genetically confirmed FH. The MI events that occurred throughout the lifespan until the last medical visit were included. The median observation period was 50 years. An exome chip genotyping method (Illumina) was used to impute the rs964184 genotype.
RESULTS
Among the 725 patients, 190 individuals carried one risk allele G (CG genotype), whereas 15 patients were carriers of the GG genotype. A significant difference in circulating triglycerides was observed between the 3 groups (1.33 [1.03-1.73] vs 1.46 [1.09-2.11] vs 1.56 [1.07-2.42] mmol/L, for the CC, CG, and GG carriers, respectively, P = .004 for the analysis of variance). The ZPR1 SNP rs964184 was significantly associated with MI even after correction for classical cardiovascular risk factors (hazard ratio 5.68, 95% confidence interval 2.40-13.45, P = .00008).
CONCLUSIONS
The cardiovascular risk in patients with FH is highly heterogeneous, and this study suggests that the rs964184 variant of the ZPR1 gene represents one of the important modulating factors.
背景
通过全基因组关联研究发现，ZPR1 基因中的 rs964184 变体与普通人群的血脂和心血管疾病风险相关，但该变体在家族性高胆固醇血症（FH）患者中的作用尚未得到研究。
目的
本研究旨在探讨 rs964184 SNP 对 FH 患者血脂和心肌梗死（MI）发病风险的影响。
方法
本研究纳入了 725 名经基因证实的 FH 患者。纳入了整个生命周期内直至最后一次就诊时发生的 MI 事件。中位观察期为 50 年。采用外显子组芯片基因分型方法（Illumina）对 rs964184 基因型进行推断。
结果
在 725 名患者中，190 名个体携带 1 个风险等位基因 G（CG 基因型），而 15 名患者为 GG 基因型携带者。3 组间循环甘油三酯水平存在显著差异（分别为 1.33[1.03-1.73]、1.46[1.09-2.11]和 1.56[1.07-2.42]mmol/L，CC、CG 和 GG 携带者，P 值为方差分析=0.004）。即使在校正了经典心血管危险因素后，ZPR1 SNP rs964184 与 MI 仍显著相关（危险比 5.68，95%置信区间 2.40-13.45，P=0.00008）。
结论
FH 患者的心血管风险高度异质，本研究表明 ZPR1 基因的 rs964184 变体是一个重要的调节因素。
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