Additive interaction between CYP2C19AA gene polymorphism and Lp(a) on the prognosis of stroke patients.

Abstract

Objective: To investigate the influence of cytochrome P450 2C19 (CYP2C19) gene polymorphism and lipoprotein (a) (Lp(a)) levels, and their interaction, on the prognosis of stroke patients.

Methods: A total of 120 stroke patients admitted to Wuming Hospital of Guangxi Medical University from January 2022 to June 2024 were retrospectively selected as the observation group. Additionally, 118 healthy people with normal outpatient physical examination indices during the same period were selected as the control group, matched for age, gender, and body mass index (BMI). Patient prognosis was assessed three months post-stroke using the modified Rankin Scale (mRS). Patients with an mRS score > 2 were classified into the poor prognosis group, while those with an mRS score ≤ 2 were categorized into the good prognosis group. Polymerase chain reaction was utilized to detect CYP2C19 gene polymorphisms. General data were compared between patients with good and poor prognoses. Multivariate logistic regression analysis was performed to identify factors influencing poor prognosis in stroke patients and to examine the interaction between CYP2C19 gene polymorphism and Lp(a) on stroke outcomes.

Results: Among 210 stroke patients, 82 (39.05%) had a poor prognosis, and 128 (60.95%) had a good prognosis. The NIHSS scores at admission of stroke patients with AA, AG, and GG genotypes increased sequentially (P < 0.05). Multivariate logistic regression analysis showed that CYP2C19 genotype and Lp(a) levels were independent factors influencing prognosis in stroke patients (both P < 0.05). The correlation between CYP2C19 gene polymorphism and stroke prognosis under additive, recessive, and dominant models showed that the CYP2C19 allele was a risk gene for poor prognosis, while the G allele was protective. Compared to the GG genotype, patients with AA or AG genotypes had a higher risk of poor prognosis (P < 0.05). Interaction analysis showed that the risk of poor prognosis in stroke patients with CYP2C19 AA genotype and Lp(a) levels in Q₂-Q₅ was 15.023 times higher than in those with good prognosis. Similarly, the risk for patients with CYP2C19 AG genotype and Lp(a) levels in Q₂-Q₅ was 6.435 times higher. After controlling for confounding factors, the relative excess risk (REPI) = 33.166 (-144.689-181.020), the attributable proportion (AP) = 0.901 (0.625-1.177), and the interaction index (S) = 13.526 (1.114-164.174), indicating an additive interaction between CYP2C19 gene polymorphism and Lp(a) on poor stroke prognosis.

Conclusion: An additive interaction exists between CYP2C19 AA gene polymorphism and Lp(a) levels in influencing stroke prognosis. Clinically, timely interventions based on these factors can improve stroke patient outcomes.