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

Autor: Donald W. Bowden, J. Jeffrey Carr, Amanda J. Cox, Barry I. Freedman, Jeremy N. Adams, Carl D. Langefeld
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Male
lcsh:Diseases of the circulatory (Cardiovascular) system
medicine.medical_specialty
Genotype
Genetic Linkage
Endocrinology
Diabetes and Metabolism
Population
030209 endocrinology & metabolism
Single-nucleotide polymorphism
Type 2 diabetes
030204 cardiovascular system & hematology
Polymorphism
Single Nucleotide
03 medical and health sciences
0302 clinical medicine
Risk Factors
Internal medicine
Diabetes mellitus
medicine
Humans
education
Subclinical infection
Original Investigation
Aged
education.field_of_study
Genetic polymorphism
biology
Haptoglobins
business.industry
Haptoglobin
Odds ratio
Middle Aged
medicine.disease
Cardiovascular disease
3. Good health
Endocrinology
Diabetes Mellitus
Type 2
lcsh:RC666-701
Cardiovascular Diseases
biology.protein
Female
Cardiology and Cardiovascular Medicine
business
Biomarkers
Zdroj: Cardiovascular Diabetology
Cardiovascular Diabetology, Vol 12, Iss 1, p 31 (2013)
ISSN: 1475-2840
Popis: 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.
Databáze: OpenAIRE
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