Abstract
PurposeA genome-wide association study of Europeans showed eNOS rs1799983 and DYRK1A rs720470 to be two stroke susceptibility loci. Hypothesizing that heritability of these polymorphisms may differ among those with different IS subtypes, we performed an observational study within a Chinese Han population.MethodsPatients with a first IS were prospectively enrolled in the Wenzhou Stroke Registry Programme from October 2016 to June 2021. Binary logistic regression was used to investigate the effects of the selected SNPs on IS. Cases with large-artery atherosclerosis (LAA), cardioembolism (CE), and small-artery occlusion (SAO) were further evaluated in subgroup analyses. The cumulative risk of IS onset according to genotype was evaluated by Kaplan-Meier survival curve and compared by log-rank test. All cases were followed for 90 days and functional outcome was estimated by the modified Rankin Scale.ResultsA total of 1798 qualified patients with IS and 756 controls were enrolled. No significant association was found between rs1799983 or rs720470 polymorphism and IS risk. According to TOAST classification, 696 (38.71%) were LAA stroke, 308 (17.13%) were SAO stroke, 496 (27.58%) were CE stroke and 298 (16.57%) were stroke of other determined or undetermined etiology. In the subgroup analysis, for rs1799983, those with GT or TT genotypes had a significantly higher risk of LAA IS compared with those with the GG genotype (co-dominant model, P = .032; dominant model, odds ratio1.451; 95% confidence interval 1.09-1.94; P = .012). Patients with the GG genotype had a significantly later LAA IS onset age compared with patients with GT or TT genotypes (log-rank test, P = .002).ConclusionThis study indicates that eNOS rs1799983 polymorphism may serve as a genetic biomarker of LAA stroke risk among Han Chinese.