Manfredi Samantha, Calvi Debora, del Fiandra Martina, Botto Nicoletta, Biagini Andrea, Andreassi Maria Grazia
National Research Council, Institute of Clinical Physiology, G Pasquinucci Hospital, Via Aurelia Sud-Montepepe, 54100 Massa, Italy.
Pharmacogenomics. 2009 Jan;10(1):29-34. doi: 10.2217/14622416.10.1.29.
Since long-term exposure to oxidative stress is strongly implicated in the pathogenesis of diabetic complications, polymorphic genes of detoxifying enzymes must be involved in the development of coronary artery disease (CAD). We assessed the potential glutathione S-transferase (GST) gene-gene (GSTM1(null)-GSTT1(null)) and gene-smoking interactions on the development of CAD in patients with Type 2 diabetes.
MATERIALS & METHODS: In a case-only design, we enrolled 231 patients with Type 2 diabetes (147 male, 66.1 +/- 9.7 years) referred to our institute for coronary angiography investigation. CAD was diagnosed if there was over 50% obstruction of one or more major vessels.
Coronary angiography revealed significant CAD in 184 patients (80%). Male gender (p < 0.001), smoking habits (p = 0.003) and GSTT1(null) genotype (p = 0.003) were significantly correlated with the increasing extent of the coronary atherosclerosis. Case-only analysis revealed that patients with both M(null)-T(null) genotypes had the highest risk for 3-vessel CAD compared with patients who express both GST genes (odds ratio: 3.1; 95% confidence interval: 1.0-10.3, p = 0.04). A nearly threefold interaction existed between cigarette smoking and M(null)-T(null) genotypes (odds ratio: 2.9, 95% confidence interval: 1.7-7.8, p = 0.03). A significant interaction between M(null)-T(null) genotypes and smoking was also observed on the increasing number of coronary vessels that were diseased (chi(2) = 14.0; p = 0.03).
These data suggest that polymorphisms in GSTM1 and GSTT1 genes are risk factors for CAD in Type 2 diabetic patients, especially among smokers. These genetic markers may permit the targeting of preventive and early intervention on high-risk patients to reduce their cardiovascular risk.
由于长期暴露于氧化应激与糖尿病并发症的发病机制密切相关，解毒酶的多态性基因必定参与了冠状动脉疾病（CAD）的发生发展。我们评估了谷胱甘肽S-转移酶（GST）基因-基因（GSTM1（无效）-GSTT1（无效））以及基因-吸烟相互作用对2型糖尿病患者CAD发生发展的影响。
在一项仅针对病例的设计中，我们纳入了231例因冠状动脉造影检查转诊至我院的2型糖尿病患者（147例男性，年龄66.1±9.7岁）。如果一根或多根主要血管阻塞超过50%，则诊断为CAD。
冠状动脉造影显示184例患者（80%）存在显著的CAD。男性（p<0.001）、吸烟习惯（p = 0.003）和GSTT1（无效）基因型（p = 0.003）与冠状动脉粥样硬化程度的增加显著相关。仅针对病例的分析显示，与同时表达两种GST基因的患者相比，同时具有M（无效）-T（无效）基因型的患者发生三支血管CAD的风险最高（比值比：3.1；95%置信区间：1.0 - 10.3，p = 0.04）。吸烟与M（无效）-T（无效）基因型之间存在近三倍的相互作用（比值比：2.9，95%置信区间：1.7 - 7.8，p = 0.03）。在病变冠状动脉血管数量增加方面，也观察到M（无效）-T（无效）基因型与吸烟之间存在显著的相互作用（χ² = 14.0；p = 0.03）。
这些数据表明，GSTM1和GSTT1基因的多态性是2型糖尿病患者发生CAD的危险因素，尤其是在吸烟者中。这些遗传标记可能有助于针对高危患者进行预防和早期干预，以降低他们的心血管风险。
