Haptoglobin genotype - A determinant of cardiovascular complication risk in type 1 diabetes
Haptoglobin genotype - A determinant of cardiovascular complication risk in type 1 diabetes
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DOI：
10.2337/db08-0095
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发表时间：
2008-06-01
期刊：
影响因子：
7.7
通讯作者：
Orchard, Trevor J.
中科院分区：
文献类型：
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作者：
Costacou, Tina;Ferrell, Robert E.;Orchard, Trevor J.
结合珠蛋白是一种血浆蛋白，可结合游离血红蛋白，从而抑制血红蛋白诱导的氧化损伤。我们调查了一组儿童期发病的1型diabetes.RESEARCH设计和方法的个人之间的结合珠蛋白基因型和冠状动脉疾病（CAD）的发病率的关联，参与者从糖尿病并发症的流行病学研究谁是免费的CAD在研究进入，并有DNA可供选择（n = 453，平均年龄27.1岁，糖尿病病程18.8年）。CAD被定义为心绞痛、缺血性心电图、心电图或医院记录中Q波证实的心肌梗死、血管造影狭窄> 50%或血管重建。在IS年随访期间，发生了135例（29.8%）CAD事件。单变量地，触珠蛋白1/1、2/1和2/2的CAD事件比例分别从15.4%增加至28.3%和34.6%（P = 0.02，P趋势= 0.007）。累积发生率（包括33例基线流行病例）也分别从24.1%增至32.3%和39.1%（P = 0.07，P趋势0.02）。在校正传统CAD风险因素的考克斯比例风险模型中，与触珠蛋白1/1基因型相比，触珠蛋白2/2基因型与CAD发病率增加相关（风险比[HR] 2.21，95%CI 1.054.65，P = 0.04）。虽然与触珠蛋白2/1基因型相关的风险没有达到显著性（1.78，0.84-3.79，P = 0.13），但在三组中仍有显著性趋势（P = 0.03）。
OBJECTIVE-Haptoglobin is a plasma protein that binds free hemoglobin, thereby inhibiting hemoglobin-induced oxidative damage. We investigated the association between the haptoglobin genotype and the incidence of coronary artery disease (CAD) in a cohort of individuals with childhood-onset type 1 diabetes.RESEARCH DESIGN AND METHODS-Participants from the Epidemiology of Diabetes Complications Study who were free of CAD at study entry and had DNA available were selected (n = 453, mean age 27.1 years, and diabetes duration 18.8 years). CAD was defined as angina, ischemic electrocardiogram, myocardial infarction confirmed by Q-waves on electrocardiogram or hospital records, angiographic stenosis >50%, or revascularization.RESULTS-The proportions of the cohort with the haptoglobin 1/1, 2/1, and 2/2 genotypes were 11.5, 41.3, and 47.2%, respectively. During IS years of follow-up, there were 135 (29.8%) incident CAD events. Univariately, the proportion of CAD events increased from 15.4 to 28.3 and 34.6% for haptoglobin 1/1, 2/1, and 2/2, respectively (P = 0.02, P-trend = 0.007). Cumulative incidence (including 33 baseline prevalent cases) also increased from 24.1 to 32.3 and 39.1%, respectively (P = 0.07, P-trend 0.02). In Cox proportional hazards models adjusting for traditional CAD risk factors, the haptoglobin 2/2 genotype was associated with increased CAD incidence compared with the haptoglobin 1/1 genotype (hazard ratio [HR] 2.21, 95% CI 1.054.65, P = 0.04). Although the risk associated with the haptoglobin 2/1 genotype did not reach significance (1.78, 0.84-3.79, P = 0.13), there remained a significant trend across the three groups (P = 0.03).CONCLUSIONS-These data support the hypothesis that the haptoglobin genotype influences cardiovascular risk in type 1 diabetes.