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锰超氧化物歧化酶(MnSOD)、谷胱甘肽过氧化物酶-1(GPX1)和过氧化氢酶(CAT)的多态性变异导致中国 2 型糖尿病或糖尿病心血管疾病患者的血浆甘油三酯水平升高。

Polymorphic variations in manganese superoxide dismutase (MnSOD), glutathione peroxidase-1 (GPX1), and catalase (CAT) contribute to elevated plasma triglyceride levels in Chinese patients with type 2 diabetes or diabetic cardiovascular disease.

机构信息

Department of Endocrinology & Metabolism, Shanghai Diabetes Institute, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.

出版信息

Mol Cell Biochem. 2012 Apr;363(1-2):85-91. doi: 10.1007/s11010-011-1160-3. Epub 2011 Dec 14.

DOI:10.1007/s11010-011-1160-3
PMID:22167619
Abstract

Manganese superoxide dismutase (MnSOD), glutathione peroxidase-1 (GPX1), and catalase (CAT) provide the primary antioxidant defense system. Impaired antioxidant defense increases oxidative stress and contributes to the development of type 2 diabetes and diabetic cardiovascular disease (CVD). We preformed a case-control study in Chinese type 2 diabetes patients, to determine if the MnSOD Val16Ala (T→C), GPX1 Pro198Leu (C→T), and CAT -262C/T (C→T) functional polymorphisms contribute to the development of type 2 diabetes or diabetic CVD. Patients with type 2 diabetes (n = 168) were divided into the non-CVD group (n = 83, >10 year since diagnosis) and CVD group (n = 85, history of ischemic CVD). Genotyping was performed using PCR-restriction fragment length polymorphism (PCR-RFLP) or PCR-based direct sequencing. The genotypic distribution in the non-CVD- and CVD-group and the clinical parameters in genotypic groups were not significantly different in the three polymorphic sites, respectively. Among eight genotypic combinations, the most common TT+CC+CC genotype (59.5%) was associated with higher triglyceride levels than the TT+CT+CC genotype, the second frequent one (14.9%; 1.77 ± 0.12 vs. 1.21 ± 0.11 mmol/l, P = 0.001), and all non-TT+CC+CC genotypes (40.5%; 1.77 ± 0.12 vs. 1.43 ± 0.12 mmol/l, P = 0.048). In the CVD group, significantly elevated triglyceride levels were also observed in patients with TT+CC+CC compared to patients with TT+CT+CC (2.00 ± 0.18 vs. 1.37 ± 0.16 mmol/l, P = 0.018) or non-TT+CC+CC genotypes (2.00 ± 0.18 vs. 1.65 ± 0.19 mmol/l, P = 0.070). The common MnSOD, GPX1, and CAT TT+CC+CC genotype may contribute to hypertriglyceridemia in Chinese patients with type 2 diabetes or diabetic CVD.

摘要

锰超氧化物歧化酶 (MnSOD)、谷胱甘肽过氧化物酶-1 (GPX1) 和过氧化氢酶 (CAT) 提供了主要的抗氧化防御系统。抗氧化防御功能受损会增加氧化应激,导致 2 型糖尿病和糖尿病心血管疾病 (CVD) 的发生。我们在中国 2 型糖尿病患者中进行了病例对照研究,以确定 MnSOD Val16Ala (T→C)、GPX1 Pro198Leu (C→T) 和 CAT-262C/T (C→T) 功能多态性是否有助于 2 型糖尿病或糖尿病 CVD 的发生。2 型糖尿病患者 (n = 168) 分为非 CVD 组 (n = 83,诊断后>10 年) 和 CVD 组 (n = 85,缺血性 CVD 病史)。采用 PCR-限制性片段长度多态性 (PCR-RFLP) 或基于 PCR 的直接测序法进行基因分型。三个多态性位点的非 CVD 组和 CVD 组的基因型分布以及基因型组的临床参数均无显著差异。在八种基因型组合中,最常见的 TT+CC+CC 基因型 (59.5%) 与较高的甘油三酯水平相关,高于 TT+CT+CC 基因型,其次是 TT+CC+CT 基因型 (14.9%;1.77 ± 0.12 vs. 1.21 ± 0.11 mmol/L,P = 0.001),以及所有非 TT+CC+CC 基因型 (40.5%;1.77 ± 0.12 vs. 1.43 ± 0.12 mmol/L,P = 0.048)。在 CVD 组中,与 TT+CT+CC 基因型 (2.00 ± 0.18 vs. 1.37 ± 0.16 mmol/L,P = 0.018) 或非 TT+CC+CC 基因型 (2.00 ± 0.18 vs. 1.65 ± 0.19 mmol/L,P = 0.070) 相比,TT+CC+CC 基因型患者的甘油三酯水平也明显升高。在中国 2 型糖尿病或糖尿病 CVD 患者中,常见的 MnSOD、GPX1 和 CAT TT+CC+CC 基因型可能导致甘油三酯升高。

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