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 18 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 1.05-4.65, 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.
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 18 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 1.05-4.65, 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.
Authors: Annie J Kruger; Chaoxing Yang; Sun W Tam; Douglas Hinerfeld; James E Evans; Karin M Green; John Leszyk; Kejian Yang; Dennis L Guberski; John P Mordes; Dale L Greiner; Aldo A Rossini; Rita Bortell Journal: Exp Biol Med (Maywood) Date: 2010-11
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Authors: David M Maahs; Justyna Siwy; Angel Argilés; Marie Cerna; Christian Delles; Anna F Dominiczak; Nathalie Gayrard; Alexander Iphöfer; Lothar Jänsch; George Jerums; Karel Medek; Harald Mischak; Gerjan J Navis; Johannes M Roob; Kasper Rossing; Peter Rossing; Ivan Rychlík; Eric Schiffer; Roland E Schmieder; Thomas C Wascher; Brigitte M Winklhofer-Roob; Lukas U Zimmerli; Petra Zürbig; Janet K Snell-Bergeon Journal: PLoS One Date: 2010-09-28 Impact factor: 3.240