Levy Andrew P, Hochberg Irit, Jablonski Kathleen, Resnick Helaine E, Lee Elisa T, Best Lyle, Howard Barbara V
Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
J Am Coll Cardiol. 2002 Dec 4;40(11):1984-90. doi: 10.1016/s0735-1097(02)02534-2.
The goal of this study was to determine if the haptoglobin phenotype was predictive of cardiovascular disease (CVD) in diabetic mellitus (DM).
Cardiovascular disease is the most frequent, severe, and costly complication of type 2 DM. There are clear geographic and ethnic differences in the risk of CVD among diabetic patients that cannot be fully explained by differences in conventional CVD risk factors. We have demonstrated that a functional allelic polymorphism in the haptoglobin gene acts as a major determinant of susceptibility for the development of diabetic microvascular complications.
We sought to determine if this paradigm concerning the haptoglobin gene could be extended to CVD in DM. We tested this hypothesis in a case-control sample from the Strong Heart study, a population-based longitudinal study of CVD in American Indians. Haptoglobin phenotype was determined by polyacrylamide gel electrophoresis in 206 CVD cases and 206 matched controls age 45 to 74 years. Median follow-up was six years.
In multivariate analyses controlling for conventional CVD risk factors, haptoglobin phenotype was a highly statistically significant, independent predictor of CVD in DM. The odds ratio of having CVD in DM with the haptoglobin 2-2 phenotype was 5.0 times greater than in DM with the haptoglobin 1-1 phenotype (p = 0.002). An intermediate risk of CVD was associated with the haptoglobin 2-1 phenotype.
This study suggests that determination of haptoglobin phenotype may contribute to the algorithm used in CVD risk stratification, and in evaluation of new therapies to prevent CVD in the diabetic patient.
本研究的目的是确定触珠蛋白表型是否可预测糖尿病（DM）患者的心血管疾病（CVD）。
心血管疾病是2型糖尿病最常见、最严重且代价高昂的并发症。糖尿病患者中CVD风险存在明显的地域和种族差异，而传统CVD风险因素的差异无法完全解释这些差异。我们已经证明，触珠蛋白基因中的功能性等位基因多态性是糖尿病微血管并发症发生易感性的主要决定因素。
我们试图确定关于触珠蛋白基因的这一模式是否可扩展至糖尿病患者的CVD。我们在美国印第安人CVD的一项基于人群的纵向研究——强心研究的病例对照样本中检验了这一假设。通过聚丙烯酰胺凝胶电泳确定了206例CVD病例和206例年龄在45至74岁的匹配对照的触珠蛋白表型。中位随访时间为6年。
在控制传统CVD风险因素的多变量分析中，触珠蛋白表型是糖尿病患者CVD的一个具有高度统计学意义的独立预测因素。患有触珠蛋白2 - 2表型的糖尿病患者发生CVD的比值比是患有触珠蛋白1 - 1表型的糖尿病患者的5.0倍（p = 0.002）。触珠蛋白2 - 1表型与CVD的中度风险相关。
本研究表明，确定触珠蛋白表型可能有助于用于CVD风险分层的算法，并有助于评估预防糖尿病患者CVD的新疗法。
