Affiliated Hospital, College of Medicine, Hebei University of Engineering, Handan 056038, PR China.
Affiliated Hospital, Hebei University of Engineering, NO. 81 and 83 Cong Tai Road, Handan 056002, PR China.
J Stroke Cerebrovasc Dis. 2020 Aug;29(8):104935. doi: 10.1016/j.jstrokecerebrovasdis.2020.104935. Epub 2020 Jun 3.
Vascular atherosclerosis leads to various cardiovascular and cerebrovascular diseases. Nitric oxide (NO) promotes vasodilatation and prevents Coronary Artery Disease (CAD). Pin1 suppresses NO production by down-regulating the activity of endothelial nitric oxide synthase (eNOS). Whether the genetic polymorphisms of the PIN1 gene (encoding Pin1) are implicated in CAD deserves investigations in human beings.
A total of 210 CAD patients and control individuals (all females) were enrolled, and their genotypes of rs2233679 (-667C/T, a key SNP in the promoter of PIN1 gene) were sequenced. T-test, chi-square test, odds ratio (OR) and 95% confidence interval (95% CI) were calculated to evaluate Hardy-Weinberg equilibrium, varied genetic distribution and relative CAD risk.
The differences in age, BMI, triglyceride, total cholesterol, low-density and high density cholesterol between the CAD and control groups were not significant (all P>0.05), and Hardy-Weinberg equilibrium was observed in the two groups (both P>0.05). The frequency of -667T allele in the CAD group was higher than that in the control group. The genotype -667TT elicited a higher hazardous risk of CAD compared to the genotype -667CC (OR=1.85, 95% CI: 0.75-4.53) as well as the genotypes CC+CT (OR=1.97, 95% CI: 0.86-4.49).
We firstly show that the allele -667T in the PIN1 promoter may elicit a higher CAD-risk than -667C, and the -667TT genotype of PIN1 may be a new genetic biomarker for increased incidence of CAD. These novel observations put forward a new understanding of the PIN1-CAD genetic relationship in humans, potentially contributing to both cardiovascular and cerebrovascular disorders.
血管动脉粥样硬化导致各种心血管和脑血管疾病。一氧化氮（NO）促进血管扩张，预防冠心病（CAD）。Pin1 通过下调内皮型一氧化氮合酶（eNOS）的活性来抑制 NO 的产生。PIN1 基因（编码 Pin1）的遗传多态性是否与 CAD 有关值得在人类中进行研究。
共纳入 210 例 CAD 患者和对照组个体（均为女性），并对其 rs2233679（PIN1 基因启动子中的关键 SNP-667C/T）的基因型进行测序。采用 T 检验、卡方检验、比值比（OR）和 95%置信区间（95%CI）评估 Hardy-Weinberg 平衡、不同遗传分布和相对 CAD 风险。
CAD 组和对照组在年龄、BMI、甘油三酯、总胆固醇、低密度和高密度胆固醇方面差异无统计学意义（均 P>0.05），两组 Hardy-Weinberg 平衡均无差异（均 P>0.05）。CAD 组-667T 等位基因频率高于对照组。与基因型-667CC 相比，基因型-667TT 发生 CAD 的危险度更高（OR=1.85，95%CI：0.75-4.53），与基因型 CC+CT 相比也更高（OR=1.97，95%CI：0.86-4.49）。
我们首次表明，PIN1 启动子中的等位基因-667T 可能比-667C 引发更高的 CAD 风险，PIN1 的-667TT 基因型可能是 CAD 发病率增加的新遗传生物标志物。这些新的观察结果为人类 PIN1-CAD 遗传关系提供了新的认识，可能有助于心血管和脑血管疾病的发生。
