CYP2C19 loss-of-function variants are independent risk factors for premature cerebral infarction: a hospital based...

Cytochrome P450 2C19 (CYP2C19) plays an vital role in the course of cardiovascular and cerebrovascular diseases by affecting lipid metabolism. Triglyceride-glucose (TyG) is a comprehensive index composed of triglyceride and blood glucose, has relationship with some diseases. There was no research report on the association CYP2C19 polymorphisms, TyG with premature cerebral infarction (CI) (onset ≤ 65 years old) susceptibility.

This study retrospectively analyzed 1953 CI patients aged ≤ 65 years old from December 2018 to March 2024, and 1919 age-matched individuals with non-CI as controls. The relationship between CYP2C19 polymorphisms, TyG and premature CI risk were analyzed.

The proportion of hypertension, and diabetes mellitus in patients with premature CI was higher than those in controls. The serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), and TyG levels in patients with premature CI were significantly higher than those in controls (all p < 0.05). The patients had lower CYP2C19 *1 allele frequency (63.3% vs. 69.6%, p < 0.001) and higher CYP2C19 *2 allele frequency (31.3% vs. 25.4%, p < 0.001) than controls. Logistic regression analysis showed that smoking history (odds ratio (OR): 1.193, 95% confidence interval (CI): 1.002-1.422, p = 0.048), hypertension (OR: 3.371, 95% CI: 2.914-3.898, p < 0.001), diabetes mellitus (OR: 1.911, 95% CI: 1.632-2.237, p < 0.001), CYP2C19 intermediate metabolizer (IM) + poor metabolizer (PM) phenotypes (OR: 1.424, 95% CI: 1.243-1.631, p < 0.001), and dyslipidemia (OR: 1.294, 95% CI: 1.077-1.554, p = 0.006) were independent risk factors for premature CI.

History of smoking, hypertension, diabetes mellitus, dyslipidemia, and CYP2C19 IM + PM phenotypes were independently associated with premature CI susceptibility.