功能丧失是早发性冠状动脉疾病的一个相关危险因素：一项病例对照研究。
Loss-of-Function is an Associated Risk Factor for Premature Coronary Artery Disease: A Case-Control Study.
作者信息
Chen Wenhao, Liu Yuanliang, Deng Xunwei, Li Bin, Wang Hao, Wei Guoliang, Chen Kehui, Wang Shen
机构信息
Center for Cardiovascular Diseases, Meizhou People's Hospital, Meizhou, People's Republic of China.
Department of Computer Tomography, Meizhou People's Hospital, Meizhou, People's Republic of China.
出版信息
Int J Gen Med. 2024 Nov 3;17:5049-5058. doi: 10.2147/IJGM.S486187. eCollection 2024.
OBJECTIVE
Cytochrome P450 2C19 (CYP2C19) is a major enzyme involved in the biotransformation and metabolism of various substances. Loss-of-function of the gene represents downregulation of CYP2C19 enzyme indication limited or no enzymatic function, which may be, in turn, associated with some disease susceptibility. The relationship between polymorphisms and susceptibility to premature coronary artery disease (PCAD) is not fully understood. This study aimed to assess this relationship.
METHODS
This study included 635 PCAD patients, and 548 age-matched non-CAD individuals as controls, from November 2019 to August 2023. The rs4244285 (681G > A, *2) and rs4986893 (636G > A, *3) were genotyped, and the distribution of polymorphisms between patients and controls and the relationship between polymorphisms and PCAD risk were analyzed.
RESULTS
A total of 442 (37.4%), 543 (45.9%), and 198 (16.7%) individuals had extensive metabolizer (EM) (*1/*1), intermediate metabolizer (IM) (*1/*2 and *1/*3), and poor metabolizer (PM) (*2/*2, *2/*3, and *3/*3) phenotypes, respectively. *2/*2 genotype frequency was higher, *1/*1 genotype was lower in PCAD patients than controls. Individuals with PM phenotype had higher triglyceride (TG) levels than those with EM or IM phenotypes. Logistic regression analysis showed that body mass index (BMI) ≥24.0 kg/m (≥24.0 kg/m vs 18.5-23.9 kg/m, odds ratio (OR): 1.326, 95% confidence interval (CI): 1.041-1.688, = 0.022), smoking (OR: 1.974, 95% CI: 1.283-3.306, = 0.002), hypertension (OR: 1.327, 95% CI: 1.044-1.687, = 0.021), diabetes mellitus (OR: 1.390, 95% CI: 1.054-1.834, = 0.020), PM phenotype (PM phenotype vs EM phenotype, OR: 1.701, 95% CI: 1.200-2.411, = 0.003), and IM+PM phenotypes (IM+PM vs EM phenotype, OR: 1.369, 95% CI: 1.077-1.740, = 0.010) were associated with PCAD.
CONCLUSION
PM or IM+PM phenotypes, overweight, smoking, hypertension, and diabetes mellitus were associated with PCAD.
目的
细胞色素P450 2C19（CYP2C19）是参与多种物质生物转化和代谢的主要酶。该基因功能丧失代表CYP2C19酶下调，表明酶功能有限或无酶功能，这反过来可能与某些疾病易感性相关。CYP2C19基因多态性与早发性冠状动脉疾病（PCAD）易感性之间的关系尚未完全明确。本研究旨在评估这种关系。
方法
本研究纳入了2019年11月至2023年8月期间的635例PCAD患者以及548例年龄匹配的非CAD个体作为对照。对rs4244285（681G>A，*2）和rs4986893（636G>A，*3）进行基因分型，并分析患者与对照之间CYP2C19基因多态性的分布以及CYP2C19基因多态性与PCAD风险之间的关系。
结果
分别有442例（37.4%）、543例（45.9%）和198例（16.7%）个体具有广泛代谢型（EM）（*1/*1）、中间代谢型（IM）（*1/2和1/*3）和慢代谢型（PM）（*2/*2、*2/3和3/3）表型。PCAD患者中2/*2基因型频率较高，*1/*1基因型频率低于对照。PM表型个体的甘油三酯（TG）水平高于EM或IM表型个体。逻辑回归分析显示，体重指数（BMI）≥24.0 kg/m²（≥24.0 kg/m² 与18.5 - 23.9 kg/m²相比，比值比（OR）：1.326，95%置信区间（CI）：1.041 - 1.688，P = 0.022）、吸烟（OR：1.974，95% CI：1.283 - 3.306，P = 0.002）、高血压（OR：1.327，95% CI：1.044 - 1.687，P = 0.021）、糖尿病（OR：1.390，95% CI：1.054 - 1.834，P = 0.020）、PM表型（PM表型与EM表型相比，OR：1.701，95% CI：1.200 - 2.411，P = 0.003）以及IM + PM表型（IM + PM与EM表型相比，OR：1.369，95% CI：1.077 -
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