Do CRP gene variants and smoking elevate recurrent stroke risk in minor ischemic stroke patients?

Abstract

Background: Minor ischemic strokes, despite their initial mild symptoms, pose a significant risk of recurrence, potentially leading to severe disability. The role of C-reactive protein (CRP) gene variants in predicting the recurrent minor stroke, particularly their interaction with lifestyle factors such as smoking, remains unclear. We aimed to investigate the relationship of single-nucleotide polymorphisms (SNPs) in CRP gene with minor stroke recurrence, focusing on gene-environment interactions.

Methods: A retrospective cohort study was conducted using data from the stroke registry at Linfen People's Hospital, including 2032 first-time minor stroke patients (NIHSS score ≤ 5) admitted within 7 days of symptom onset from January 2019 to December 2022. Follow-up assessments were conducted every 3 months for one year. Based on recurrence during follow-up, participants were classified into Recurrence and Non-recurrence group. Genomic DNA was extracted for genotyping four CRP gene SNPs: rs1130864, rs1800947, rs2808632, and rs3093059. Genetic associations with the stroke recurrence were analyzed using additive, dominant, recessive genetic and allelic models. Generalized Multifactor Dimensionality Reduction (GMDR) was employed to explore the complex interaction of these SNPs with smoking status. Multivariate logistic regression was used to estimate the strength of these associations.

Results: Our study recruited 261 participants who experienced recurrent minor strokes and 264 age- and sex-matched controls without recurrence. The A allele of rs2808632 (P = 0.002) and C allele of rs3093059 (P = 0.001) were significantly associated with an increased risk of stroke recurrence. Participants with the combined genotypes rs2808632 CA + AA and rs3093059 TC + CC had a 1.325-fold higher risk of recurrence when compared to those with the genotypes rs2808632 CC and rs3093059 TT (P = 0.003). Additionally, among smokers, the rs3093059 TC + CC genotypes were associated with a 2.467-fold increased risk of recurrence compared to non-smokers with TT genotype (P < 0.001).

Conclusion: The rs2808632 and rs3093059 polymorphisms independently and interactively contribute to an increased risk of recurrent minor stroke. Furthermore, the interaction between rs3093059 SNP and smoking status significantly influenced stroke recurrence, highlighting the importance of considering both genetic and environmental factors in predicting the risk of minor stroke recurrence.