Zhang Zhizhong, Xu Gelin, Zhu Wusheng, Cao Liping, Yan Bernard, Liu Xinfeng
Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, 305# East Zhongshan Road, Nanjing, 210002, Jiangsu Province, China.
Melbourne Brain Centre, Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia.
Mol Neurobiol. 2015 Dec;52(3):1648-1653. doi: 10.1007/s12035-014-8964-6. Epub 2014 Nov 5.
A recent genome-wide association study (GWAS) identified a nonsynonymous SNP (1425G/A) in PRKCH which was associated with increased risk of ischemic stroke. The purpose of this study was to examine whether this functional polymorphism is associated with stroke onset and prognosis in a Chinese population. We genotyped PRKCH 1425G/A using Improved Multiple Ligase Detection Reaction in 919 patients with ischemic stroke. Analyses of genotype association with onset and prognosis outcomes were assessed by the Kaplan-Meier method, the log-rank test, and the Cox proportional hazards models. PRKCH 1425G/A was not associated with age of stroke onset (P = 0.323). However, this functional polymorphism was significantly associated with risk of stroke recurrence in recessive models (hazard ratio [HR] = 2.23; 95% confidential interval [CI], 1.06 to 4.68; P = 0.014), and this effect was more predominant among smokers (HR = 3.67; 95% CI, 1.47-9.18; P = 0.005). Moreover, the variant genotypes of PRKCH 1425G/A are an independent prognostic factor for ischemic stroke in the final multivariate Cox regression model. Our findings show that PRKCH 1425G/A may be a useful biomarker for predicting the recurrence of ischemic stroke.
最近一项全基因组关联研究(GWAS)在蛋白激酶C eta(PRKCH)中鉴定出一个非同义单核苷酸多态性(SNP)(1425G/A),其与缺血性中风风险增加相关。本研究的目的是检验这种功能性多态性是否与中国人群的中风发病及预后相关。我们采用改良多重连接检测反应对919例缺血性中风患者的PRKCH 1425G/A进行基因分型。通过Kaplan-Meier法、对数秩检验和Cox比例风险模型评估基因型与发病及预后结果的关联。PRKCH 1425G/A与中风发病年龄无关(P = 0.323)。然而,这种功能性多态性在隐性模型中与中风复发风险显著相关(风险比[HR] = 2.23;95%置信区间[CI]为1.06至4.68;P = 0.014),且这种效应在吸烟者中更为显著(HR = 3.67;95% CI为1.47 - 9.18;P = 0.005)。此外,在最终的多变量Cox回归模型中,PRKCH