Association of genetic variant rs3662C＞A in the gene of p21-activated kinase 2 with risk and prognosis of stroke as well as its effect on transcription activity

Abstract

Objective To identify the relationship between variant rs3662C＞A in the gene of p21-activated kinase 2 (PAK2) and risk of stroke as well as prognosis, and to explore the effect of rs3662C＞A on the transcriptional activity of PAK2 gene. Methods In a multi-center case-control study including 733 cerebral atherothrombotic stroke, 488 lacunar infarction, 435 intracerebral hemorrhage and 1 727 healthy controls, the relationship between variant and risk of three stroke subtypes was examined using the multivariate logistic regression model. The stroke patients were prospectively followed up for a median of 4.5 years, and the relationship between rs3662 and cardiovascular events as well as mortality was analyzed using the Cox proportional-hazards model. The effect of rs3662C＞A on the transcriptional activity of PAK2 gene was examined using the luciferase reporter assays. Results The rs3662A allele was associated with a decreased risk of atherosclerotic stroke as compared with rs3662CC genotype, and odds ratio was 0.67 (95% CI: 0.47~0.95,P＜0.05) in a dominant genetic model. This relationship had sex-specific difference and was significant incline to male. During the follow-up, atherosclerotic stroke patients carrying with rs3662A allele had a significantly higher risk of cardio-cerebrovascular events and cardiovascular mortality; hazards ratio was respectively 1.84 (95% CI: 1.16~2.92,P＜0.05) and 2.06 (95% CI:1.05~4.04,P＜0.05). The rs3662C significantly reduced the luciferase activity by 79% (P＜0.01). Conclusions The carriers with rs3662A allele of PAK2 gene have a reduced risk for atherosclerotic stroke but a worse prognosis. It is found that rs3662A affects the PAK2 expression level.

Keywords

• p21-activated kinase 2(pak2)|genetic variants|susceptibility|stroke|prognosis