浙江南部地区人群5-脂氧合酶激活蛋白和磷酸二酯酶4D基因突变与缺血性脑卒中的研究

Correlation between ALOX5AP and PDE4Dgenes mutation and cerebral ischemic stroke in populations of Southern Zhejiang Province

目的为探索浙江南部地区人群5-脂氧合酶激活蛋白(ALOX5AP)基因中SG13S89、SG13S114和磷酸二酯酶4D(PDE4D)基因中单核苷酸多态性83与缺血性脑卒中的关系。方法选择脑梗死患者394例为脑梗死组,另选无脑梗死382例为对照组。采用PCR和基质辅助激光解析/电离飞行时间质谱法,分析ALOX5AP基因中的SG13S89(rs4769874)、SG13S114(rs10507391)和PDE4D基因中单核苷酸多态性83(rs966221)的多态性。结果与对照组比较,脑梗死组SG13S89基因AG型、A等位基因频率明显升高(4.1%vs 1.3%,P<0.05;2.0%vs0.7%,P<0.05);。多因素logistic回归分析显示,调整高血压、糖尿病和年龄后,SG13S89的AG基因型相对于GG基因型有较高的脑卒中风险(OR=4.24,95%CI:1.17～15.32,P=0.027)。SG13S89等位基因分布与大动脉粥样硬化型和小动脉闭塞型脑梗死差异无统计学意义(P>0.05)。SG13S89的AG基因型与女性人群发生脑卒中相关(P=0.022),但A等位基因在女性脑卒中人群中差异无统计学意义(P>0.05)。结论 rs4769874AG基因型和A等位基因频率可增高缺血性脑卒中风险,可能是该基因与血管炎性反应和通透性增加导致脑梗死的机制相关。但未发现PDE4D基因单核苷酸多态性83突变与脑卒中相关。

Objective To study the correlation between SNP83 of ALOX5AP （SG13S89 and SG13Sl14） and PDE4D genes and cerebral ischemie stroke （CIS） in populations of Southern Zhe- jiang Province. Methods Three hundred and ninety-four CIS patients served as a CIS group and 382 non-CIS subjects served as a control group in this study. The SNP83 （rs966221） of SG13S89 （rs4769874） ,SG13Sl14 （rs10507391） and PDE4D genes was analyzed by PCR and matrix-assisted laser desorption/ionization time of flight, respectively. Results The frequency of SG13S89 AG genotype and A allele was significantly higher in CIS group than in control group （4. 1% vs 1.3%,P〈0.05 ;2.0% vs 0. 7%,P〈0.05）. Multivariate logistic regression analysis showed that the SG13S89 AG genotype was a higher risk for CIS than the SG13S89 GG genotype after adjust- ment for hypertension, DM and age （OR = 4.24,95 % CI ： 1.17 -- 15.32, P= 0.027 ）. The SG 13 S89 AG genotype was related with CIS in female populations （P=0. 022）. However, no significant difference was found in the A allele of female populations （P〉0.05）. Conclusion The frequency of ALOX5AP genotype and A allele increases the risk of CIS by promoting vascular inflammation and permeability. SNP83 of the PDE4D gene is not related with CIS.