Nutrition, Metabolism and Atherosclerosis Clinic, Institut de recherches cliniques de Montréal, Québec, Canada.
Nutrition, Metabolism and Atherosclerosis Clinic, Institut de recherches cliniques de Montréal, Québec, Canada; Department of Nutrition, Université de Montréal, Québec, Canada.
J Clin Lipidol. 2018 Jul-Aug;12(4):966-971. doi: 10.1016/j.jacl.2018.04.012. Epub 2018 Apr 30.
Familial hypercholesterolemia (FH) is the most frequent autosomal codominant disease worldwide and is characterized by elevated low-density lipoprotein cholesterol and premature coronary artery disease (CAD). Polymorphisms in phosphatase and actin regulator 1 (PHACTR1) have been shown to be associated with cardiovascular risk in large genome-wide association studies studies.
The aim of the present study is to evaluate the association between the rs12526453 polymorphism in the PHACTR1 gene and the prevalence of CAD in FH patients.
A cohort of 668 adult genetically confirmed heterozygous FH subjects were included in the present study. Logistic regression models were used to evaluate the strength of the association between rs12526453 genotype and CAD prevalence.
Noncarriers (CC) of the rs12526453 represented 41% of the cohort, whereas heterozygous (CG) and homozygous (GG) carriers represented 44% and 15%, respectively. The prevalence of CAD was significantly higher in non-carriers of the rs12526453 polymorphism compared to heterozygous and homozygous carriers (38.0%, 25.8%, 24.5%, respectively, P = .001). When a dominant logistic regression model was studied, the association between this single-nucleotide polymorphism and CAD prevalence was significant even after correction for all classical cardiovascular risk factors (odds ratio 0.48, 95% confidence intervals 0.31-0.74, P = .001).
In the present study, we have shown that the rs12526453 single-nucleotide polymorphism of the PHACTR1 gene is significantly associated with a 50% reduction in the odds of CAD events in FH subjects. Because the protective G allele is frequent in the Caucasian population (allelic frequency of 0.26), screening for this polymorphism in Caucasian FH subjects could further help to stratify risk of CAD in this population.
家族性高胆固醇血症（FH）是全球最常见的常染色体显性疾病，其特征是低密度脂蛋白胆固醇升高和早发冠心病（CAD）。磷酸酶和肌动蛋白调节因子 1（PHACTR1）中的多态性已被证明与大基因组关联研究中的心血管风险相关。
本研究旨在评估 PHACTR1 基因中 rs12526453 多态性与 FH 患者 CAD 患病率之间的关联。
本研究纳入了 668 名经基因确认的杂合子 FH 成年患者。使用逻辑回归模型评估 rs12526453 基因型与 CAD 患病率之间的关联强度。
rs12526453 的非携带者（CC）占队列的 41%，而杂合子（CG）和纯合子（GG）携带者分别占 44%和 15%。与杂合子和纯合子携带者相比，rs12526453 多态性的非携带者 CAD 患病率显著更高（分别为 38.0%、25.8%、24.5%，P=.001）。当研究显性逻辑回归模型时，即使在对所有经典心血管危险因素进行校正后，该单核苷酸多态性与 CAD 患病率之间的关联仍然显著（比值比 0.48，95%置信区间 0.31-0.74，P=.001）。
在本研究中，我们表明 PHACTR1 基因的 rs12526453 单核苷酸多态性与 FH 患者 CAD 事件发生风险降低 50%显著相关。由于保护的 G 等位基因在白种人群中较为常见（等位基因频率为 0.26），在白种 FH 患者中筛查该多态性可能有助于进一步分层该人群的 CAD 风险。
