The Association Between Chromosome 10q25 Polymorphism And Large Artery Atherosclerotic Stroke

Background and aims:Ischemic stroke is a major cause of mortality and disability worldwide,loading heavy economic burden.In most cases,loci detected in Genome-wide association study(GWAS)were attributed to a specific subtype of ischemic stroke,which suggests the different heritability of stroke subtypes and the necessity of subtype-specific studies.Recently,a GWAS in European population demonstrated that the rs11196288,a single nucleotide polymorphism(SNP)located on chromosome 10q25 near HABP2 gene,was significantly associated with early-onset(age<60 years)ischemic stroke overall and most subtypes of ischemic stroke.The HABP2 gene,which encodes factor VII-activating protease(FSAP),has been proved to be related to inflammatory pathways,stroke,late complications of carotid stenosis and atherosclerotic plaque instability.And the interaction between genetic and environmental factors,such as age,has also received increasing attention.Here we performed this study to investigate the association between the rs11196288A>G polymorphism and large artery atherosclerotic(LAA)stroke risk in the Chinese Han population and to validate whether age interacts rs11196288 to influence the risk of LAA stroke.Methods:Genotyping of rs11196288 was performed in blood samples of 1066 LAA stroke patients and 1167 healthy controls.Univariate and multivariate logistic regression analyses were used to assess the effect of the rs11196288A>G polymorphism on the susceptibility and short-term outcome of LAA stroke.Nomograms were developed based on results from the multivariate logistic models to estimate the probability future risk and poor functional outcome of LAA stroke for an individual participant.Results:A significant decrement of LAA stroke risk was found in co-dominant(AG vs.AA,OR=0.76,95%CI= 0.64-0.91,P= 0.003;GG vs.AA,OR= 0.65,95%CI=0.50-0.85,P=0.002),dominant(AG/GG vs.AA,OR=0.74,95%Cl=0.62-0.87,P<0.001)and recessive models(GG vs.AA/AG,OR= 0.76,95%CI=0.59-0.97,P=0.028)of rs11196288.However,there was no significant interaction between age and genotypes of rs11196288(P>0.05),regardless of genetic model.And no significant association was observed between the rs11196288A>G polymorphism and short-term outcome of LAA stroke(P>0.05).Conclusions:In the southeastern Chinese population,the rs11196288A>G polymorphism is associated with decreased risk of LAA stroke.