Genetic analysis of haptoglobin polymorphisms with cardiovascular disease and type 2 diabetes in the diabetes heart study

Cardiovascular Diabetology

Original Investigation

Donald W Bowden¹  Amanda J Cox¹  Barry I Freedman²  J Jeffrey Carr³  Carl D Langefeld⁴  Jeremy N Adams⁵ 

[1] Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, 27157, Winston-Salem, North Carolina, USA;Center for Diabetes Research, Wake Forest School of Medicine, 27157, Winston-Salem, North Carolina, USA;Department of Biochemistry, Wake Forest School of Medicine, Medical Center Boulevard, 27157, Winston-Salem, North Carolina, USA;Department of Internal Medicine – Nephrology, Wake Forest School of Medicine, 27157, Winston-Salem, North Carolina, USA;Department of Radiologic Sciences, Wake Forest School of Medicine, 27157, Winston-Salem, North Carolina, USA;Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest School of Medicine, 27157, Winston-Salem, North Carolina, USA;Molecular Genetics and Genomics Program, Wake Forest School of Medicine, 27157, Winston-Salem, North Carolina, USA;Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, 27157, Winston-Salem, North Carolina, USA;Center for Diabetes Research, Wake Forest School of Medicine, 27157, Winston-Salem, North Carolina, USA;

关键词: Haptoglobin;    Genetic polymorphism;    Cardiovascular disease;    Type 2 diabetes;   

DOI  :  10.1186/1475-2840-12-31

 received in 2012-11-12, accepted in 2013-02-01,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundHaptoglobin (HP) is an acute phase protein that binds to freely circulating hemoglobin. HP exists as two distinct forms, HP1 and HP2. The longer HP2 form has been associated with cardiovascular (CVD) events and mortality in individuals with type 2 diabetes (T2DM).MethodsThis study examined the association of HP genotypes with subclinical CVD, T2DM risk, and associated risk factors in a T2DM-enriched sample. Haptoglobin genotypes were determined in 1208 European Americans (EA) from 473 Diabetes Heart Study (DHS) families via PCR. Three promoter SNPs (rs5467, rs5470, and rs5471) were also genotyped.ResultsAnalyses revealed association between HP2-2 duplication and increased carotid intima-media thickness (IMT; p = 0.001). No association between HP and measures of calcified arterial plaque were observed, but the HP polymorphism was associated with triglyceride concentrations (p = 0.005) and CVD mortality (p = 0.04). We found that the HP2-2 genotype was associated with increased T2DM risk with an odds ratio (OR) of 1.49 (95% CI 1.18-1.86, p = 6.59x10-4). Promoter SNPs were not associated with any traits.ConclusionsThis study suggests association between the HP duplication and IMT, triglycerides, CVD mortality, and T2DM in an EA population enriched for T2DM. Lack of association with atherosclerotic calcified plaque likely reflect differences in the pathogenesis of these CVD phenotypes. HP variation may contribute to the heritable risk for CVD complications in T2DM.

【 授权许可】

Unknown   
© Adams et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.