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

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