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Cardiovascular Diabetology

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Open Access 01-12-2013 | Original investigation

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

Authors: Jeremy N Adams, Amanda J Cox, Barry I Freedman, Carl D Langefeld, J Jeffrey Carr, Donald W Bowden

Published in: Cardiovascular Diabetology | Issue 1/2013

Abstract

Background

Haptoglobin (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).

Methods

This 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.

Results

Analyses 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.

Conclusions

This 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.

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Title: Genetic analysis of haptoglobin polymorphisms with cardiovascular disease and type 2 diabetes in the diabetes heart study
Authors: Jeremy N Adams
Amanda J Cox
Barry I Freedman
Carl D Langefeld
J Jeffrey Carr
Donald W Bowden
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Cardiovascular Diabetology / Issue 1/2013
Electronic ISSN: 1475-2840
DOI: https://doi.org/10.1186/1475-2840-12-31

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