Abstract
BackgroundContribution of cardiovascular disease related genetic risk factors for stroke are not clearly defined. We performed a genetic association study to assess the association of 56 previously characterized gene variants in 34 candidate genes from cardiovascular disease related biological pathways with ischemic stroke and cerebral hemorrhage in a Chinese population.MethodsThere were 1280 stroke patients (1101 with ischemic stroke and 179 with cerebral hemorrhage) and 1380 controls in the study. The genotypes for 56 polymorphisms of 34 candidate genes were determined by the immobilized probe approach and the associations of gene polymorphisms with ischemic stroke and cerebral hemorrhage were performed by logistic regression under an allelic model.ResultsAfter adjusting for age, sex, BMI and hypertension status by logistic regression analysis, we found that NPPA rs5063 was significantly associated with both ischemic stroke (odds ratio [OR] 0.69; 95% confidence interval [CI], 0.52 to 0.90; P = 0.006) and cerebral hemorrhage(OR = 0.39; 95%CI, 0.19 to 0.78; P = 0.007). In addition, MTHFR rs1801133 also was associated with cerebral hemorrhage (OR = 1.48; 95%CI, 1.16 to1.89; P = 0.001) but not with ischemic stroke (OR = 1.08; 95%CI, 0.96 to1.22; P = 0.210). After false discovery rate (FDR) correction, the association of NPPA rs5063 and MTHFR rs1801133 with cerebral hemorrhage remained significant.ConclusionsThe NPPA rs5063 is associated with reduced risk for cerebral hemorrhage and MTHFR rs1801133 is associated with increased risk of cerebral hemorrhage in a Chinese population.
Highlights
Stroke is one of the leading causes of mortality and disability in the world [1]
methylenetetrahydrofolate reductase (MTHFR) rs1801133 was associated with cerebral hemorrhage
NPPA rs5063 was associated with cerebral hemorrhage and marginally associated with ischemic stroke
Summary
Stroke is one of the leading causes of mortality and disability in the world [1]. In China, about 1.5 to 2 million new strokes occur every year [2], [3], there are 58–142 per 100,000 people each year who die of stroke in China [4]. Data from the China Multicenter Collaborative Study of Cardiovascular Epidemiology showed that on average, the proportion of cerebral hemorrhage was one third and the proportion of ischemic stroke was two thirds in Chinese populations [5]. Many candidate genes have been studied for a potential role in stroke. Contribution of cardiovascular disease related genetic risk factors for stroke are not clearly defined. We performed a genetic association study to assess the association of 56 previously characterized gene variants in 34 candidate genes from cardiovascular disease related biological pathways with ischemic stroke and cerebral hemorrhage in a Chinese population
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