Potential risk modifications of GSTT1, GSTM1 and GSTP1 (glutathione-S-transferases) variants and their association to CAD in patients with type-2 diabetes
Potential risk modifications of GSTT1, GSTM1 and GSTP1 (glutathione-S-transferases) variants and their association to CAD in patients with type-2 diabetes
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DOI：
10.1016/j.bbrc.2011.02.097
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发表时间：
2011-04-01
影响因子：
3.1
通讯作者：
Selvam, Govindan Sadasivam
中科院分区：
文献类型：
--
作者：
Ramprasath, Tharmarajan;Murugan, Ponniah Senthil;Selvam, Govindan Sadasivam
背景：2型糖尿病（T2 DM）是冠心病（CAD）的主要危险因素，导致高发病率和死亡率。谷胱甘肽S-转移酶（GSTM 1、GSTT 1和GSTP 1）以其广泛的解毒作用和异生物质的代谢而闻名。近年来的研究发现GST基因变异与2型糖尿病和冠心病的关系。本病例对照研究中，我们确定了GST变异与2型糖尿病患者发生CAD的相关性。方法：我们从印度南部招募了222例2型糖尿病患者，290例2型糖尿病合并CAD患者和270例年龄、性别和来源相匹配的健康对照。测量血清脂质谱，并从血液样品中提取DNA。对研究参与者进行GSTM 1/T1（无效多态性）和GSTP 1（105 A > G）的多重PCR用于基因分型。对基因频率和血脂谱进行统计学分析。GSTM 1缺失基因型与2倍增加相关（OR = 2.925; 95% CI = 2.078-4.119; P < 0.0001），CSTT 1缺失基因型与3倍增加相关（OR = 3.114; 95% CI = 2.176-4.456; P < 0.0001）。GSTP 1基因型Ile/瓦尔和瓦尔/瓦尔与2型糖尿病的发病风险也有显著性差异（OR = 1.423，CI = 1.041-1.946; P=0.027和OR = 1.829，CI = 1.064-3.142; P = 0.029）。增加的比值比显示GSTT 1-null基因型在T2 DM合并CAD患者中的发生率高于无CAD的T2 DM患者（OR = 1.918，95%CI = 1.144-3.214; P = 0.014）。与对照组和T2 DM患者相比，GSTT 1基因型患者的HDL水平显著低于GSTT 1基因型患者（43.50 +/- 4.10 vs. 45.20 +/- 3.90; P = 0.004）。然而，LDL水平显示GSTT 1-null基因型比GSTT 1-present基因型显著增加（108.70 +/- 16.90 vs. 102.20 +/- 12.60; P = 0.005）。在T2 DM和T2 DM合并CAD患者中，尽管GSTM 1-null多态性与血脂水平无相关性，但GSTT 1-null多态性与LDL水平有统计学意义（127 +/- 28.20 vs. 134 +/- 29.10; P = 0.039）和甘油三酯（182.10 +/- 21.10 vs. 191.20 +/- 24.10; P = 0.018）。我们的工作得出结论，GSTM 1，GSTT 1和GSTP 1变异体可能促进T2 DM的发展，GSTT 1变异体单独参与T2 DM相关CAD并发症的发展。南印度人口。(C)2011 Elsevier Inc. All rights reserved.
Background: Type-2 diabetes mellitus (T2DM) is a major risk factor for coronary artery disease (CAD) resulting in high morbidity and mortality. Glutathione S-transferases (GSTM1, GSTT1 and GSTP1) are known for their broad range of detoxification and in the metabolism of xenobiotics. Recent studies revealed the relationship of GSTs variants with T2DM and CAD. In this case-control study we ascertained the association of GSTs variants in association with the development of CAD in patients with T2DM.Methods: From the Southern part of India, we enrolled 222 T2DM patients, 290 T2DM patients with CAD and 270 healthy controls matched for age, sex and origin. Serum lipid profiles were measured and DNA was extracted from the blood samples. Multiplex PCR for GSTM1/T1 (null polymorphism) and PCR-RFLP for GSTP1 (105 A > G), were performed for genotyping of study participants. Gene frequency and lipid profiles were statistically analyzed for disease association.Results: Regression analysis showed that. GSTM1-null genotype is associated with a 2-fold increase (OR = 2.925; 95% CI = 2.078-4.119; P < 0.0001) and CSTT1-null genotype is associated with a 3-fold increase (OR = 3.114; 95% CI = 2.176-4.456; P < 0.0001) to T2DM development. Ile/Val and Val/Val genotypes of GSTP1 also showed a significant risk for T2DM (OR = 1.423, CI = 1.041-1.946; P=0.027 and OR = 1.829, CI = 1.064-3.142; P = 0.029). Increased odds ratio showed that GSTT1-null genotype had a moderately higher occurrence in T2DM-CAD patients (OR = 1.918, 95% CI = 1.144-3.214; P = 0.014) than T2DM patients without CAD. The level of HDL has significantly decreased in GSTT1-present than in GSTT1-null genotype (43.50 +/- 4.10 vs. 45.20 +/- 3.90; P = 0.004) when compared with control and T2DM patients. However, LDL level showed a significant increase in GSTT1-null than GSTT1-present genotype (108.70 +/- 16.90 vs. 102.20 +/- 12.60; P = 0.005). Although the GSTM1-null polymorphism showed no correlation with lipid profiles among T2DM and T2DM with CAD patients, GSTT1-null polymorphism attained a statistical significance for the level of LDL (127 +/- 28.20 vs. 134 +/- 29.10; P = 0.039) and triglycerides in T2DM with CAD patients (182.10 +/- 21.10 vs. 191.20 +/- 24.10; P = 0.018).Conclusion: Our work concludes that GSTM1, GSTT1 and GSTP1 variants might contribute to the development of T2DM and GSTT1 variant alone is involved in the development of T2DM associated CAD complications in the South Indian population. (C) 2011 Elsevier Inc. All rights reserved.