对氧磷酶1192Gln/Arg和对氧磷酶2311Cys/Ser多态性与2型糖尿病合并大血管病变的相关性

The Association of Paraoxonase-1 192 Gln/Arg and Paraoxonase-2 311 Cys/Ser Gene Polymorphisms with Macrovascular Disease in Type 2 Diabetes Mellitus Patients

目的探讨对氧磷酶1基因192 Gln/Arg和对氧磷酶2基因311 Cys/Ser多态性与山东青岛地区2型糖尿病患者合并大血管病变的关系。方法通过抽提基因组DNA并应用聚合酶链反应检测对氧磷酶1 192 Gln/Arg和对氧磷酶2 311 Cys/Ser多态性在2型糖尿病合并大血管病变组、单纯2型糖尿病组以及正常对照组的基因频率。联合分析两种基因变异在2型糖尿病合并大血管病变的发病中有无协同效应。结果山东青岛地区人群存在对氧磷酶1 192 Gln/Arg和对氧磷酶2 311 Cys/Ser多态性。2型糖尿病合并大血管病变组与单纯2型糖尿病组和正常对照组比较对氧磷酶1的3种基因型（QQ、QR、RR）的构成比差异无显著性,而对氧磷酶2的3种基因型（CC、CS、SS）的构成比差异有显著性（P〈0.05或P〈0.01）,S等位基因频率较其他两组显著增高（P〈0.05或P〈0.01）。联合分析发现对氧磷酶2 311 S等位基因是2型糖尿病合并大血管病变的独立危险因素,当对氧磷酶2 311 S等位基因与对氧磷酶1 192 R等位基因并存时,患2型糖尿病合并大血管病变的相对危险度明显增加（OR=49.494,95%CI为0.907-2701.872）。结论在山东青岛地区人群中,对氧磷酶2 311 Cys/Ser多态性与2型糖尿病合并大血管病变具有相关性,其S等位基因可能是该地区2型糖尿病合并大血管病变的危险因素之一。当同时检测出对氧磷酶1 192 R等位基因时对2型糖尿病合并大血管病变更具有预测或诊断价值。

Aim To investigate the association between paraoxonase-2 gene 311 Cys/Ser polymorphism and macrovaseular disease in combination with paraoxonase-1 gene 192 GlrdArg polymorphisan in type 2. diabetes mellitus patients. Methods A ease-control study of 272 Chinese subjects was performet. Genomie DNA was extracted from the subjects＇ peripheral blood leukocytes. The paraoxonase-1 gene 192 GlrdArg and paraoxonase-2 gene 311 Cys/Ser polymorphisms were determined by PCR analysis. In addition, the association was investigated between paraoxonase-2 gene 311 Cys/Ser polymorphism and maerovaseular disease in combination wifla paraoxonase- 1 gene 192 GlrdArg polymorplfism in control group and type 2 diabetes mellitus complicated witli macrovascular disease group. Results Paraoxonase-1 gene 192 Gln/Arg and paraoxonase-2 gene 311 Cys/Ser polymorphisms were detected in population of Qingdao. The genetype distribution （QQ, QR and RR） of paraoxonase-1 gene 192 Gln/Arg polymorphism showed no significant differences between type 2 diabetes mellitus complicated with macrovascular disease group and the other two groups（type 2 diabetes mellitus group ＆ healthy subjects）. But the genetype distribution （CC,＇CS and SS ） of paraoxonase-2 gene 311 Cys/Ser polymorphism showed significant differences between type 2 diabetes mellitus complicated with maerovascular disease group and the other two groups, the former had a significantly lfigher S allele frequency （ P 〈 0.05 or P 〈 0.01 ）. The linkage analysis of pmaoxonase-2 gene 311 Cys/Ser and paraoxonase-1 gene 192 Gln/Arg gene polymorphisms further emphasized that paraoxonase-2 gene 311 S allele was an independent risk factor leading to type 2 diabetes mellitus complicated with maerovascular disease. Wben both of the paraoxonase-2 gene 311 S allele and the paraoxonase-1 gene 192 R allele existed, tire OR of paraoxonase-2 gene 311 S allele for type 2 diabetes nreUitus complicated with maerovascular disease was significandy higher （OR= 49.494, 95%CI： 0.907- 2 701.872）. Condusions The paraoxonase-2 gene 311 Cys/Ser polymorphism is associated with type 2 diabetes meUitus complicated with macrovasctdar disease in Qingdao＇s population. S allele may be a risk factor for type 2 diabetes meUitus complicated with macrovascular disease. Meanwhile, detecting the paraoxonase-I gene 192 R allele may provide a more precise method to predict or diagnose type 2 diabetes meUitus complicated with macrovascular disease.