Genetic association of glutathione peroxidase-1 with coronary artery calcification in type 2 diabetes: a case control study with multi-slice computed tomography.
Genetic association of glutathione peroxidase-1 with coronary artery calcification in type 2 diabetes: a case control study with multi-slice computed tomography.
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DOI：
10.1186/1475-2840-6-23
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发表时间：
2007-09-07
影响因子：
9.3
通讯作者：
Tajima N
中科院分区：
文献类型：
--
作者：
Nemoto M;Nishimura R;Sasaki T;Hiki Y;Miyashita Y;Nishioka M;Fujimoto K;Sakuma T;Ohashi T;Fukuda K;Eto Y;Tajima N
虽然糖尿病中活性氧（ROS）积累引起的氧化应激已变得明显，但仍不清楚哪些参与氧化还原平衡的基因决定糖尿病动脉粥样硬化发生的易感性。本研究评估了产生或负责减少ROS的酶的遗传多态性对2型糖尿病（T2 D）冠状动脉钙化的影响。冠状动脉硬化的指标，冠状动脉钙化评分（CACS）评价91 T2 D患者使用多层计算机断层扫描。对患者的ROS清除酶、谷胱甘肽过氧化物酶-1（GPx-1）、过氧化氢酶、Mn-SOD、Cu/Zn-SOD以及作为ROS促进元件的NADPH氧化酶的SNP、与T2 D发作相关的基因（CAPN 10、ADRB 3、PPAR γ、FATP 4）进行基因分型。对年龄、血压、BMI、HbA 1c、血脂和糖尿病病程进行多因素回归分析。GPx-1基因Pro/Leu基因型的CACS显著高于Pro/Pro基因型（分别为744 ± 1，291 vs. 245 ± 399，p = 0.006）。此外，当检测偏离Hardy-Weinberg平衡时，CACS ≥ 1000的患者的Pro/Leu基因型频率显著高于CACS < 1000的患者（45.5% vs. 18.8%; OR = 3.61，CI = 0.97-13.42; p = 0.045）。多元回归分析显示CACS与GPx-1基因型和年龄显著相关。GPx-1基因的Pro 197 Leu取代的存在可能在决定T2 D患者冠状动脉粥样硬化的遗传易感性方面发挥关键作用。该机制可能与GPx-1变异体抑制ROS的能力降低有关。
Although oxidative stress by accumulation of reactive oxygen species (ROS) in diabetes has become evident, it remains unclear what genes, involved in redox balance, would determine susceptibility for development of atherosclerosis in diabetes. This study evaluated the effect of genetic polymorphism of enzymes producing or responsible for reducing ROS on coronary artery calcification in type 2 diabetes (T2D). An index for coronary-arteriosclerosis, coronary artery calcium score (CACS) was evaluated in 91 T2D patients using a multi-slice computed tomography. Patients were genotyped for ROS-scavenging enzymes, Glutathione peroxidase-1 (GPx-1), Catalase, Mn-SOD, Cu/Zn-SOD, as well as SNPs of NADPH oxidase as ROS-promoting elements, genes related to onset of T2D (CAPN10, ADRB3, PPAR gamma, FATP4). Age, blood pressure, BMI, HbA1c, lipid and duration of diabetes were evaluated for a multivariate regression analysis. CACS with Pro/Leu genotype of the GPx-1 gene was significantly higher than in those with Pro/Pro (744 ± 1,291 vs. 245 ± 399, respectively, p = 0.006). In addition, genotype frequency of Pro/Leu in those with CACS ≥ 1000 was significantly higher than in those with CACS < 1000 (45.5% vs. 18.8%; OR = 3.61, CI = 0.97–13.42; p = 0.045) when tested for deviation from Hardy-Weinberg's equilibrium. Multivariate regression analyses revealed that CACS significantly correlated with GPx-1 genotypes and age. The presence of Pro197Leu substitution of the GPx-1 gene may play a crucial role in determining genetic susceptibility to coronary-arteriosclerosis in T2D. The mechanism may be associated with a decreased ability to scavenge ROS with the variant GPx-1.
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影响因子：
3.5
作者：
Ohnuki, K;Yoshida, S;Andou, T
通讯作者：
Andou, T
影响因子：
11.1
作者：
Ukkola, O;Erkkilä, PH;Kesäniemi, YA
通讯作者：
Kesäniemi, YA
影响因子：
5.3
作者：
Jiang, ZW;Akey, JM;Jin, L
通讯作者：
Jin, L
影响因子：
30.8
作者：
Horikawa, Y;Oda, N;Bell, GI
通讯作者：
Bell, GI
DOI：
10.1161/01.atv.0000163846.51473.09
发表时间：
2005-07-01
影响因子：
8.7
作者：
Leopold, JA;Loscalzo, J
通讯作者：
Loscalzo, J