Lack of association between polymorphisms of catalase, copper-zinc superoxide dismutase (SOD), extracellular SOD and endothelial nitric oxide synthase genes and macroangiopathy in patients with type 2 diabetes mellitus
Lack of association between polymorphisms of catalase, copper-zinc superoxide dismutase (SOD), extracellular SOD and endothelial nitric oxide synthase genes and macroangiopathy in patients with type 2 diabetes mellitus
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DOI：
10.1046/j.1365-2796.2001.00828.x
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发表时间：
2001-05-01
影响因子：
11.1
通讯作者：
Kesäniemi, YA
中科院分区：
文献类型：
--
作者：
Ukkola, O;Erkkilä, PH;Kesäniemi, YA
目的探讨过氧化氢酶、铜锌超氧化物歧化酶（Cu/Zn-SOD）和细胞外超氧化物歧化酶（EC-SOD）基因多态性与2型糖尿病大血管病变的关系。还确定了内皮一氧化氮合酶（eNOS）基因的错义Glu 298 Asp变体的患病率及其与大血管病的相关性。设计。横断面研究。设置。北芬兰欧卢大学医院周围地区。主题和方法。共筛选了239例2型糖尿病患者和245例对照受试者。采用聚合酶链反应（PCR）技术进行基因分型。冠心病的诊断依据临床和心电图标准。根据临床标准评估脑血管病（CVD）和周围血管病（PVD）的患病率，并在医院实验室进行实验室分析。抗氧化酶基因型分布和等位基因频率在2型糖尿病患者和对照组之间无差异。eNOS基因型和等位基因频率在糖尿病患者和对照组中也相似，接近英国人群中早期报道的频率。这些多态性与大血管或微血管病变或高血压无关。男性糖尿病患者中，eNOS Asp 298 Asp基因型者血浆极低密度脂蛋白胆固醇（VLDL）和VLDL-甘油三酯（TG）浓度高于Glu 298 Glu或Glu 298 Asp基因型者（P < 0.01）。过氧化氢酶、Cu/Zn SOD和EC-SOD基因多态性与2型糖尿病患者心血管疾病无关。eNOS Glu 298 Asp变异与男性糖尿病患者血浆中含VLDL的脂蛋白相关，但与大血管病变无关。研究结果不支持关键抗氧化酶的多态性可能是解释2型糖尿病患者大血管病变高患病率的因素之一的观点。
Objectives, The association between the polymorphisms of three different antioxidative enzyme catalase, copper-zinc superoxide dismutase (Cu/Zn-SOD) and extracellular superoxide dismutase (EC-SOD)-genes and macroangiopathy was examined in patients with type 2 diabetes mellitus. The prevalence of the missense Glu298Asp variant of the endothelial nitric oxide synthase (eNOS) gene and its association with macroangiopathy were also determined.Design. Cross-sectional study.Setting. District around Oulu University Hospital, North Finland.Subjects and methods. A total of 239 patients with type 2 diabetes mellitus and 245 control subjects were screened. Genotypes were determined by polymerase chain reaction (PCR) technique. The diagnosis of coronary heart disease (CHD) was based on clinical and ECG criteria. The prevalences of cerebrovascular (CVD) and peripheral vascular diseases (PVD) were assessed on the basis of clinical criteria, Laboratory analyses were carried out in the hospital laboratory.Results. No differences in the genotype distributions and allele frequencies of the antioxidative enzymes were found between type 2 diabetes mellitus patients and controls. The eNOS genotypes and allele frequencies were also similar in the diabetic patients and controls being close to that reported earlier in the British population None of the polymorphisms were associated with macro- or microangiopathy or hypertension. However, male diabetic patients with eNOS Asp298Asp genotype had higher plasma very; low density lipoprotein (VLDL) cholesterol and VLDL-triglyceride concentrations than those with the genotypes Glu298Glu or Glu298Asp (P < 0.01 for trend).Conclusions. The polymorphism of catalase, Cu/Zn SOD and EC-SOD genes were not related to cardiovascular disease in type 2 diabetes mellitus patients. The eNOS Glu298Asp variant was associated with plasma VLDL-containing lipoproteins but not with macroangiopathy in diabetic male patients. The findings do not support the notion that the polymorphisms of the key antioxidative enzymes could be amongst the factors that explain the high prevalence of macroangiopathy in patients with type 2 diabetes mellitus.