摘要目的 探讨分泌型卷曲相关蛋白1(SFRP1)基因多态性及基因-吸烟交互作用与大动脉粥样硬化(LAA)型脑梗死的关系.方法 选取2016年8月至2017年6月在青岛大学附属医院神经内科就诊的LAA型脑梗死患者264例(脑梗死组)和同期健康体检者228名(对照组),采用聚合酶链反应-限制性片段长度多态性结合DNA测序技术,检测SFRP 1基因(rs7832767、rs1127379、rs3242)的基因型.使用Logistic回归模型分析SFRP 1基因多态性与LAA型脑梗死的关系;使用交互作用相加模型评价SFRP 1基因-吸烟交互作用与LAA型脑梗死的关系.结果 脑梗死组rs7832767位点的TT/CT基因型及T等位基因频率明显高于对照组[分别为54.9％ (145/264)和37.7％ (86/228),OR=2.123,95％ CI1.482～3.041,P＜0.01;33.9％(179/528)和20.0％(91/456),OR=2.057,95％ CI1.536 ～2.755.P＜0.01];rs1127379和rs3242位点的基因型及等位基因频率在脑梗死组和对照组之间差异无统计学意义.多因素Logistic回归分析示rs7832767位点TT/CT基因型是LAA型脑梗死的危险因素(OR=1.649,95％ CI1.066 ～2.550,P=0.025).进一步亚组分析显示SFRP 1基因多态性和LAA型脑梗死患者血管狭窄部位无关.交互作用分析显示rs7832767位点和吸烟之间存在相加交互作用(超额相对危险度比=2.442,95％ CI0.281～4.603);rs7832767位点携带T等位基因并且吸烟的个体罹患LAA型脑梗死的风险明显增加(OR=3.252,95％ CI1.629 ～6.491,P=0.001).未发现rs1127379、rs3243位点和吸烟之间存在交互作用.结论 SFRP 1基因rs7832767位点T等位基因可能是LAA型脑梗死的遗传易患基因;rs7832767位点与吸烟交互作用能明显增加LAA型脑梗死的风险.

abstractsObjective To investigate the impact of secreted frizzled-related protein 1 (SFRP 1) gene polymorphisms and gene-smoking interactions on the risk of large artery atherosclerotic (LAA) stroke.Methods Two hundred and sixty-four patients diagnosed with LAA stroke and 228 healthy controls were enrolled from the Department of Neurology,Affiliated Hospital of Qingdao University from August 2016 to June 2017.The methods of polymerase chain reaction-restriction fragment length polymorphism,combined with DNA sequencing,were used to detect the three single nucleotide polymorphisms (SNPs:rs7832767,rs1127379,rs3242) in the 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 The genotype TT/CT and allele T of rs7832767 in case group were in higher frequency than that in controls (54.9％ (145/264) vs 37.7％ (86/228),OR =2.123,95％ CI 1.482-3.041,P ＜0.01;33.9％ (179/528) vs 20.0％ (91/456),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.Multivariate 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).Moreover.SFRP 1 gene was not related to the distribution of cerebralvascular stenosis in LAA stroke patients.Additive model analysis showed significant interactions between rs7832767 and smoking (relative excess risk of interaction =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).Whereas,no significant interaction was detected between rs3242 or rs1127379 and smoking.Conclusion The T allele of rs7832767 within SFRP 1 gene may be a risk factor of LAA stroke,and the interactions between rs7832767 and smoking can significantly increase the risk of LAA stroke.