Sun Lingli, Tian Ling, Xu Jian, Zhang Zhizhong, Liu Xinfeng
Department of Neurology, Jinling Hospital, Medical School of Nanjing University, 305# East Zhongshan Road, Nanjing, 210002, Jiangsu Province, China.
Molecular Oncology Research Institute, Tufts Medical Center, Tufts University, Boston, MA, USA.
Mol Neurobiol. 2017 Jul;54(5):3388-3394. doi: 10.1007/s12035-016-9903-5. Epub 2016 May 12.
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.
近期全基因组关联研究已在4号染色体4q25区域鉴定出两个变异体rs10033464和rs2200733,它们与缺血性中风风险显著相关。我们开展本研究以调查这两个变异体是否与中国人群缺血性中风的发病年龄及预后相关。采用改良多重连接酶检测反应对rs10033464和rs2200733进行基因分型。采用单因素方差分析比较各变异体的缺血性中风发病平均年龄。然后估计这两个变异体对缺血性中风发病年龄的联合效应。采用Kaplan-Meier法、对数秩检验和Cox比例风险回归模型评估这两个变异体对缺血性中风预后的影响。本研究共纳入914例缺血性中风患者。rs10033464和rs2200733与缺血性中风复发无关(P>0.05)。然而,rs10033464的TT基因型与缺血性中风的早期发病显著相关(GG型为60.76岁,GT型为61.74岁,TT型为55.47岁,TT型与GT型比较:P=0.043)。联合效应分析显示,缺血性中风发病的平均年龄随着遗传风险评分的增加而降低(P=0.038)。研究结果表明,4号染色体4q25区域的变异体可能与缺血性中风的早期发病有关。有必要在其他人群中开展进一步的大规模研究以验证我们的结果。