Impact Of SFRP 1 Gene Polymorphisms And Gene-smoking Interaction On The Risk Of Large Artery Atherosclerotic Ischemic Stroke

Objective:To investigate the impact of secreted frizzled-related protein 1(SFRP 1)gene polymorphisms and on the risk of large artery atherosclerotic(LAA)stroke and the distribution of cerebralvascular stenosis in northern China.We further investigate the association between SFRP 1 gene-smoking interactions and the risk of LAA stroke.Methods:Two hundred and sixty-four patients diagnosed with LAA stroke and 228 healthy controls were enrolled from Department of Neurology,Affiliated Hospital of Qingdao University in August 2016 to June 2017.According to the distribution of atherosclerotic stenosis,the patients were divided into three groups,including intracranial angiostenosis(ICAS)group,extracranial angiostenosis(ECAS)group,and intracranial-extracranial angiostenosis(IC-ECAS)group.The methods of polymerase chain reaction-restriction fragment length polymorphism,combined with DNA sequencing,were used to detect the three single nucleotide polymorphisms(SNP rs7832767,rs1127379,rs3242)in the SFRP 1gene.Hardy–Weinberg equilibrium(HWE)was assessed using chi-square test.Pearson’s χ2test or Fisher’s exact test were applied to compare the frequencies of different genotypes and alleles in SFRP 1 gene.Logistic regression was applied to analyze associations between SNPs and LAA stroke.Cross analysis of additive model was used to evaluate gene-smoking interactions.Results:1.The genotype TT/CT and allele T of rs7832767 in case group were in higher frequency than that in controls(54.9% vs 37.7%,OR=2.123,95%CI 1.482-3.041,P<0.01;33.9% vs 20.0%,OR=2.057,95%CI 1.536-2.755,P<0.01).However,the frequencies of genotypes and alleles in other SNPs(rs1127379,rs3242)showed no significant differences between cases and controls.Mμltivariate logistic regression analysis showed that TT/CT genotype was a risk factor for LAA stroke(OR=1.649,95%CI 1.066-2.550,P=0.025).What’s more,a significant increased risk for LAA stroke was observed for patients in cigarette smoking status(OR=1.887,95%CI 1.170~3.046,P=0.009).Additionally,hypertension,diabetes,level of LDL and BMI are independent risk factors for LAA stroke as well.2.The incidence of ICAS and IC-ECAS in LAA stroke patients were 37.12% and39.12% respectively,being obviously higher than the incidence of ECAS(23.86%).Moreover,SFRP 1 gene was not related to the distribution of cerebralvascular stenosis in LAA stroke patients(P>0.05).3.Additive model analysis showed significant interactions between rs7832767 and smoking(RERI=2.442,95%CI 0.281-4.603).Smokers with T allele of rs7832767 showed significantly increased risk of LAA stroke(OR=3.252,95%CI 1.629-6.491,P=0.001).Besides,no significant interactions was detected between rs3242 or rs1127379 and smoking.Conclusions:1.The T allele of rs7832767 within SFRP 1 gene may be a risk factor of LAA stroke in northern China.2.The interactions exsit between rs7832767 and smoking,which can significantly increased the risk of LAA stroke.3.The three SNPs polymorphisms in SFRP 1 gene were not associated with the distribution of atherosclerotic stenosis in LAA stroke patients.