CYP2C19 intermediate and poor metabolizer statuses may be associated with coronary atherosclerosis among patients with type 2 diabetes mellitus

TL;DR

This study found that certain genetic variations in CYP2C19 may increase the risk of coronary atherosclerosis in patients with type 2 diabetes.

Contribution

The study identifies a novel association between CYP2C19 intermediate and poor metabolizer statuses and coronary atherosclerosis in type 2 diabetes patients.

Findings

CYP2C19 intermediate and poor metabolizer phenotypes were more frequent in patients with coronary atherosclerosis.

Logistic regression analysis showed a significant association between CYP2C19 IM/PM phenotype and coronary atherosclerosis risk.

Dyslipidemia was more common in patients with coronary atherosclerosis compared to controls.

Abstract

Type 2 diabetes mellitus (T2DM) has a higher risk of coronary atherosclerosis (CAS) compared to the general population. Cytochrome P450 2C19 (CYP2C19) closely related to the occurrence and development of cardiovascular diseases. This study intends to conduct research on the relationship between CYP2C19 polymorphisms ((rs4244285, 681G > A, *2) and (rs4986893, 636G > A, *3)) and the risk of CAS in patients with T2DM. 4,627 T2DM patients from January 2019 to March 2024 were retrospectively analyzed, included 2,390 cases of T2DM complicated with CAS and 2,237 cases of patients with T2DM only. CYP2C19 was divided into three phenotypes: extensive metabolizer (EM), intermediate metabolizer (IM), and poor metabolizer (PM) based on rs4244285 and rs4986893 SNPs. The relationship between CYP2C19 polymorphisms and CAS risk was analyzed. There were 1,403(30.3%) patients with dyslipidemia, and dyslipidemia (41.1% vs. 18.8%, p < 0.001) in patients with CAS was higher than those in controls. The frequencies of CYP2C19 IM and PM phenotypes in CAS patients were higher than those in controls. Logistic regression analysis showed that advanced age (odds ratio (OR): 1.273, 95% confidence interval (CI): 1.099–1.473, p = 0.001), overweight (OR: 1.175, 95% CI: 1.039–1.328, p = 0.010), smoking (OR: 1.238, 95% CI: 1.049–1.462, p = 0.012), alcoholism (OR: 1.445, 95% CI: 1.040–2.007, p = 0.028), hypertension (OR: 1.229, 95% CI: 1.047–1.442, p = 0.012), dyslipidemia (OR: 3.027, 95% CI: 2.641–3.469, p < 0.001), CYP2C19 IM/PM phenotype(IM + PM vs. EM phenotype, OR: 1.290, 95% CI: 1.140–1.459, p < 0.001) were associated with CAS in T2DM. CYP2C19 IM + PM phenotypes, advanced age, overweight, history of smoking, history of alcoholism, hypertension, and dyslipidemia may be associated with CAS in T2DM.

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