Key result
The CYP2C19 poor metabolizer phenotype was significantly associated with premature coronary artery disease compared to the extensive metabolizer phenotype (OR 1.701; 95% CI 1.200-2.411; p=0.003).
Why the study?
The relationship between CYP2C19 polymorphisms and susceptibility to premature coronary artery disease is not fully understood.
Are CYP2C19 loss-of-function polymorphisms associated with an increased risk of premature coronary artery disease?
Case-Control (n=1,183)
Are CYP2C19 loss-of-function polymorphisms associated with an increased risk of premature coronary artery disease?
Odds Ratio: 1.701 (95% CI 1.2–2.411)
p-value: p=0.003
CYP2C19 loss-of-function polymorphisms (PM and IM phenotypes) are associated with an increased risk of premature coronary artery disease.
May link CYP2C19 poor metabolizer status to premature CAD risk; hypothesis-generating and should not yet change practice.
Objective: Cytochrome P450 2C19 (CYP2C19) is a major enzyme involved in the biotransformation and metabolism of various substances. Loss-of-function of the CYP2C19 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 CYP2C19 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 CYP2C19 rs4244285 (681G > A, *2) and rs4986893 (636G > A, *3) were genotyped, and the distribution of CYP2C19 polymorphisms between patients and controls and the relationship between CYP2C19 polymorphisms and PCAD risk were analyzed. Results: A total of 442 (37.4%), 543 (45.9%), and 198 (16.7%) individuals had CYP2C19 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. CYP2C19 *2/*2 genotype frequency was higher, *1/*1 genotype was lower in PCAD patients than controls. Individuals with CYP2C19 PM phenotype had higher triglyceride (TG) levels than those with CYP2C19 EM or IM phenotypes. Logistic regression analysis showed that body mass index (BMI) ≥ 24.0 kg/m 2 (≥ 24.0 kg/m 2 vs 18.5– 23.9 kg/m 2 , odds ratio (OR): 1.326, 95% confidence interval (CI): 1.041– 1.688, p = 0.022), smoking (OR: 1.974, 95% CI: 1.283– 3.306, p = 0.002), hypertension (OR: 1.327, 95% CI: 1.044– 1.687, p = 0.021), diabetes mellitus (OR: 1.390, 95% CI: 1.054– 1.834, p = 0.020), CYP2C19 PM phenotype (PM phenotype vs EM phenotype, OR: 1.701, 95% CI: 1.200– 2.411, p = 0.003), and CYP2C19 IM+PM phenotypes (IM+PM vs EM phenotype, OR: 1.369, 95% CI: 1.077– 1.740, p = 0.010) were associated with PCAD. Conclusion: CYP2C19 PM or IM+PM phenotypes, overweight, smoking, hypertension, and diabetes mellitus were associated with PCAD.
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Chen et al. (2024) conducted a case-control in Premature coronary artery disease (n=1,183). CYP2C19 poor metabolizer (PM) phenotype vs. CYP2C19 extensive metabolizer (EM) phenotype was evaluated on Premature coronary artery disease (OR 1.701, 95% CI 1.200-2.411, p=0.003). The CYP2C19 poor metabolizer phenotype was significantly associated with premature coronary artery disease compared to the extensive metabolizer phenotype (OR 1.701; 95% CI 1.200-2.411; p=0.003).
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