对氧磷脂酶-1基因多态性与脑梗死的相关性研究

Correlation between paraoxonase-1 gene polymorphism and cerebral infarct

目的探讨福建地区汉族人群动脉硬化性脑梗死患者血清对氧磷脂酶-1(PON-1)活性及其基因多态性与脑梗死的关系。方法把研究对象分为脑梗死组和对照组,用分光光度法检测这两组研究对象血清对氧磷脂酶-1(PON-1)活性,同时检测血浆氧化低密度脂蛋白(OX-LDL)、高密度脂蛋白胆固醇(HDL-C)的变化,并把这些指标与PON-1的活性作相关分析。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测PON-1 192RR与55LL基因的多态性,用Logistic回归分析脑梗死组及对照组的基因型与其他危险因素的相关性。数据采用t检验及x^2检验。结果脑梗死组和对照组的PON-1活性均在已报道的中国人正常范围内,与对照组相比,脑梗死组血清PON-1活性明显降低(t=2.2142,P<0.05)。相关分析表明血PON-1活性与血OX-LDL呈负相关(r =-0.339,P<0.01),差异具有统计学意义,血PON-1活性与HDL-C无相关性。PCR结果表明PON-1 192基因的多态性在脑梗死组与对照组有明显不同,其中脑梗死组的RR基因型分布频率明显高于对照组(31.3% vs 24.6%,P=0.01,x^2=5.74),而PON-155基因的多态性在两组间差异无统计学意义(78.13% vs 76.78%,P=0.29,x^2=1.1)。分析还表明PON-1 192RR基因型的PON-1活性低于其它PON-1基因型,差异有统计学意义(P<0.001)。Logistic回归分析提示PON-1 192RR基因型是脑梗死的危险因素(OR=1.8,95% CI 0.16～5.08),高血压也是脑梗死的危险因素,而PON-155LL基因型可能不是脑梗死的危险因素。PON-1基因型与PON-1活性在高血压与非高血压组之间的差异无统计学意义。结论脑梗死组血清PON-1活性明显低于对照组,而且PON-1 192RR基因型分布频率高与对照组,与此同时,PON-1 192RR基因型的PON-1活性低于其它PON-1基因型,提示脑梗死组血清PON-1活性及PON-1 192RR基因多态性与脑梗死的发生有关,而高血压是脑梗死的独立危险因素。

Objective To study the relationship between paraoxonase-1 （PON-1） activity with its genic polymorphism and cerebral infarct in the Han nationality of Fujian Province. Method The subjects in this study included cerebral infarct group （ n = 127） and control group （ n = 128）. PON-1 activity was measured with spectrometric method in 127 patients with cerebral infarct and 128 controls, plasma oxidized low density lipoprotein （OX-LDL） and high - density lipoprotein cholesterol （HDL-C） were determined, and the correlation between PON-1 activity and OX-LDL, and HDL-C were analyzed. PON-1 192/55 genotype were determined using polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） method. The correlation between PON-1 genotypes and other risk factors were analyzed with Logistic regression analysis in cerebral infarct group and control group. The evaluating results were analyzed by t test and χ^2 test. Results PON-1 activity was lower in cerebral infarct group than that in normal controls （ t = 2.2142, P 〈 0.05）, and was negatively correlated with plasma OX-LDL （ r = - 0.339, P 〈 0.01）, and was not related with serum HDL-C. The frequency of PON-1 192RR genotype was significantly increased in cerebral infarct group compared with normal controls （31.3% vs. 24.6 % P = 0.01, χ^2 = 5.74）. The PON-1 activity in PON-1 192RR genotype was significantly lower than that of other PON-1 genotypes, Logistic regression analysis showed that hypertension （OR = 2.04, 95% CI 1.24 to 3.36） and PON-1 192RR genotype （OR= 1.8, 95%CI 0.16 to 5.08） were risk factors of cerebral infarct. No significant difference was found between patients and normal controls in regard to the genic polymorphism of PON-1 55. The differences of PON-1 genotypes and their activities between hypertensive and non-hypertensive groups were not significant. Conclusions PON-1 192RR genotype is associated with the cerebral infarct. Hypertension is the independent risk factor of cerebral infarct.