皮质下缺血性血管病与对氧磷酶1基因多态性的相关性研究

Study on the correlation between subcortical ischemic vascular disease and paraoxonase 1 gene polymorphisms

目的探讨皮质下缺血性血管病(SIVD)与对氧磷酶1(PON1)基因多态性的相关性。方法纳入65例SIVD患者和同期35例体检者分别为SIVD组和对照组,依据头颅MRI表现评定Fazekas分级及腔梗(LI)数量,将SIVD组分为WML组和LI组,并根据脑损伤程度分别分为轻度病变组、中度病变组和重度病变组,采用Sanger测序法测定受试者PON1基因分别在第192和55位点的表达。结果①SIVD组的平均年龄高于对照组(P<0.05),高密度脂蛋白胆固醇(HDL-C)水平低于对照组(P<0.05),SIVD组和对照组的吸烟状况差异有统计学意义(P<0.05);②SIVD组与对照组Q192R、L55M基因型分布均符合Hardy-Weinberg平衡定律;③SIVD组与对照组PON1基因Q192R和L55M基因型分布差异均有统计学意义(χ^(2)=8.780,P<0.05;χ^(2)=4.239,P<0.05),SIVD组R等位基因频率和M等位基因频率均高于对照组(χ^(2)=8.765,P<0.01;χ^(2)=4.926,P<0.05);④在WML组和LI组中,重度病变组R等位基因频率均高于中度病变组和轻度病变组(P<0.0167),中度病变组和重度病变组的M等位基因频率均高于轻度病变组(P<0.0167);⑤多因素Logistic回归分析显示:年龄、吸烟以及携带PON1基因R、M等位基因,均为SIVD发病风险的独立危险因素(P<0.05)。结论SIVD的发病可能与PON1基因在第192和55位点上表达的差异有关,携带该位点R、M等位基因可能对SIVD的发病有一定的促进作用,为寻找SIVD防治新的靶点提供一定的理论依据。

Objective To investigate the correlation between subcortical ischemic vascular disease(SIVD)and paraoxonase 1(PON1)gene polymorphism.Methods Sixty-five SIVD patients and 35 medical examiners in the same period were included as SIVD group and control group,respectively.The Fazekas classification and the number of luminal infarcts(LI)were evaluated according to the MRI findings of the head,and the SIVD group was divided into the WML group and the LI group.According to the degree of brain damage,they were divided into mild disease group,moderate disease group and severe disease group.Sanger sequencing method was used to determine the expression of the subject′s PON1 gene at locus 192 and 55 respectively.Results①The average age was higher than that of the control group(P<0.05),and the high-density lipoprotein cholesterol(HDL-C)level was lower than that of the control group(P<0.05).There was a statistically significant difference in smoking status between the SIVD group and the control group(P<0.05);②The distribution of Q192R and L55M genotypes in the SIVD group and the control group conformed to the Hardy-Weinberg equilibrium law;③The difference of PON1 gene Q192R and L55M genotype distribution between the SIVD group and the control group was statistically significant(χ^(2)=8.780,P<0.05;χ^(2)=4.239,P<0.05).Both the R allele frequency and M allele frequency in the SIVD group were higher than those in the control group(χ^(2)=8.765,P<0.01;χ^(2)=4.926,P<0.05);④In the WML group and the LI group,the R allele frequency of the severe disease group was higher than that of the moderate disease group and the mild disease group(P<0.0167),and the M allele frequency of the moderate disease group and the severe disease group were both higher than that of mild disease group(P<0.0167);⑤Multivariate Logistic regression analysis showed that age,smoking,and carrying PON1 gene R and M alleles were all independent risk factors for the risk of SIVD(P<0.05).Conclusion The pathogenesis of SIVD may be related to the difference in the expression of the PON1 gene at locus 192 and 55.Carrying R and M alleles at this locus may promote the pathogenesis of SIVD.These findings provide a certain theoretical basis for finding new targets for the prevention and treatment of SIVD.