Center for Research in Genetics and Genomics - CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, Colombia.
School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia.
Vasc Health Risk Manag. 2021 Nov 3;17:689-699. doi: 10.2147/VHRM.S330766. eCollection 2021.
Paraoxonase-1 (PON1), a glycoprotein associated with serum high-density lipoprotein (HDL), has a central role in metabolizing lipid peroxides, exhibiting antiatherogenic properties. The polymorphism p.Q192R has been previously associated with coronary artery disease (CAD) susceptibility and clopidogrel response.
We aimed at investigating the association of PON1 p.Q192R with CAD and clopidogrel response in Colombian population.
The study was conducted among 163 patients diagnosed with CAD and treated with clopidogrel. The allele frequencies for the PON1 192Q and 192R alleles were determined in cases and Latin-American controls obtained from the public database gnomAD (n = 17,711). Response to clopidogrel was determined by assessing the platelet function using the INNOVANCE PFA-200 System. We determined the association between PON1 p.Q192R polymorphism, increased susceptibility to CAD and high on-treatment platelet reactivity (HPR) by using odds ratio (OR) and 95% confidence interval (CI) on four genetic models.
The allele frequencies for the PON1 192Q and 192R alleles were 0.60 and 0.40, respectively. The allele distribution was found to be statistically different from the control group and other ethnic groups. The allele 192R was positively associated with decreased susceptibility to CAD under a dominant model (OR, 0.58; 95% CI, 0.42-0.8; P < 0.01). We found no association between the polymorphism and HPR.
We propose that PON1 p.Q192R is a potentially useful marker for CAD susceptibility in the Colombian population and lacks association with HPR under clopidogrel treatment.
载脂蛋白 1（PON1）是一种与血清高密度脂蛋白（HDL）相关的糖蛋白，在代谢脂质过氧化物方面发挥着核心作用，具有抗动脉粥样硬化特性。先前的研究表明，PON1 的 p.Q192R 多态性与冠心病（CAD）易感性和氯吡格雷反应相关。
我们旨在研究 PON1 p.Q192R 与哥伦比亚人群 CAD 和氯吡格雷反应的相关性。
该研究纳入了 163 例诊断为 CAD 并接受氯吡格雷治疗的患者。通过从公共数据库 gnomAD（n = 17711）中获取的病例和拉丁美洲对照，确定了 PON1 192Q 和 192R 等位基因的等位基因频率。通过使用 INNOVANCE PFA-200 系统评估血小板功能，确定氯吡格雷的反应。我们使用 4 种遗传模型的比值比（OR）和 95%置信区间（CI）来确定 PON1 p.Q192R 多态性与 CAD 易感性增加和治疗中血小板高反应性（HPR）之间的关系。
PON1 192Q 和 192R 等位基因的等位基因频率分别为 0.60 和 0.40。PON1 192 等位基因的分布与对照组和其他种族群体存在统计学差异。在显性模型下，等位基因 192R 与 CAD 易感性降低呈正相关（OR，0.58；95%CI，0.42-0.8；P < 0.01）。我们没有发现该多态性与 HPR 之间的关联。
我们提出 PON1 p.Q192R 是哥伦比亚人群 CAD 易感性的一个潜在有用的标志物，并且在氯吡格雷治疗下与 HPR 无关。
