Chromosome 4q25 Variants and Age at Onset of Ischemic Stroke

Recent genome-wide association studies have identified two variants rs10033464 and rs2200733 on chromosome 4q25, significantly associated with ischemic stroke risk. We conducted this study to investigate whether these two variants were associated with age at onset and prognosis of ischemic stroke in a Chinese population. Genotyping of rs10033464 and rs2200733 was performed by improved multiple ligase detection reaction. One-way ANOVA was used to compare the mean age of ischemic stroke onset for each variant. Combined effects of these two variants on age at ischemic stroke onset were then estimated. Kaplan-Meier method, log-rank test, and the Cox proportional hazards regression models were used to assess the effect of the two variants on ischemic stroke prognosis. A total of 914 ischemic stroke patients were included in the study. Rs10033464 and rs2200733 were not associated with ischemic stroke recurrence (P > 0.05). However, rs10033464 TT genotype was significantly correlated with early age of ischemic stroke onset (60.76 for GG, 61.74 for GT, 55.47 for TT, TT vs. GT: P = 0.043). Combined effects analysis revealed that mean age at ischemic stroke onset decreased with increasing genetic risk score (P = 0.038). The findings indicated that the chromosome 4q25 variants might associate with early age at onset of ischemic stroke. Further larger studies in other populations are warranted to validate our results.