糖尿病周围神经病变与内皮型一氧化氮含酶基因、终末糖化产物受体基因、对氧磷酶基因及醛糖还原酶基因多态性的关联研究  

An association study of diabetic neuropathy with polymorphisms of eNOS, PON1, RAGE and ALR2 Genes

作　　者：任滕[1] 项坤三[1] 刘丽梅[1] 

机构地区：[1]交通大学附属第六人民医院糖尿病研究所,上海200233

出　　处：《上海医学》2003年第1期24-27,共4页Shanghai Medical Journal

摘　　要：目的　明确终末糖化产物受体基因 (RAGE)的Gly82Ser多态、对氧磷酶基因 (PON1)的Gln191Arg多态及Leu5 4Met多态、内皮型一氧化氮合酶基因 (eNOS)的Glu2 98Asp多态以及醛糖还原酶基因 (ALR2 ) 5′端上游的二核苷酸 (CA)n串联重复序列多态与糖尿病周围神经病变的关系。方法　采用PCR RFLP及放射自显影技术对 83名健康人和 2 11例糖尿病患者的上述多态进行病例对照 关联研究。结果　①糖尿病周围神经病变与eNOS基因Glu2 98Asp多态、PON1基因Leu5 4Met多态以及RAGE基因Gly82Ser多态均不相关 (P >0 .0 5 ) ;②PON1基因Gln191Arg多态的B等位基因频率及BB基因型频率随着糖尿病周围神经病变的进展呈降低趋势(趋势分析 ,P =0 .196 ) ,等位基因频率在伴 /不伴糖尿病微血管病变组间差异有显著性 (P =0 .0 4 6 ) ,进一步分析显示这种差异主要来源于糖尿病视网膜病变 ;③ALR2基因 5′上游 (CA)n二核苷酸串联重复序列多态的Z +6等位基因频率在不伴糖尿病周围神经病变组中较伴有周围神经病变组中高 ,两者间差异有显著性 (P =0 .0 38)。④以糖尿病周围神经病变为应变量 ,各基因多态为自变量进行Logistic回归分析后显示 ,各个基因多态与糖尿病周围神经病变均无独立相关。Objective To study the association of diabetic neuropathy with eNOS Glu298Asp, PON1 Gln191Arg and Leu54Met, RAGE Gly82Ser, and (CA)n dinucleatide repeat polymorphism at 5' upstream of aldose reductase gene. Methods A case control study was carried out with PCR RFLP and radioautograph in 83 non diabetics and 211 diabetics. Results ① No significant association was found between diabetic neuropathy and eNOS Gly298Asp polymorphism, PON1 Leu54Met, and RAGE Gly82Ser polymorphisms ( P >0.05); ② The frequencies of the B allele and BB genotype of the PON1 Gln191Arg were decreased with advancement of neuropathy ( P for trend=0.196). There was a significant difference of allele distribution of PON1 Gln191Arg between groups with and without microangiopathy, and further analysis showed that this difference should be attributed to diabetic retinopathy; ③ The frequency of Z+6 allele of the 5' ALR2 was significantly higher in patients without neuropathy than that in patients with neuropathy ( P =0.038); ④None of these polymorphisms was an independent causative factor when carrying out by logistic regression analysis in diabetic neuropathy as dependent variable and the polymorphisms as independent variable. Conclusion All these genes do not play redominaut role in the pathogenesis of diabetic neuropathy.

关 键 词：糖尿病神经病变 ENOS基因 PON1基因 RAGE基因 醛糖还原酶基因 

分 类 号：R587.2[医药卫生—内分泌]