Impact of HDL genetic risk scores on coronary artery calcified plaque and mortality in individuals with type 2 diabetes from the Diabetes Heart Study.

Raffield LM, Cox AJ, Hsu FC, Ng MC, Langefeld CD, Carr JJ, Freedman BI, Bowden DW
Cardiovasc Diabetol. 2013 12: 95

PMID: 23799899 · PMCID: PMC3695806 · DOI:10.1186/1475-2840-12-95

BACKGROUND - Patients with type 2 diabetes (T2D) are at elevated risk for cardiovascular disease (CVD) events and mortality. Recent studies have assessed the impact of genetic variants affecting high-density lipoprotein cholesterol (HDL) concentrations on CVD risk in the general population. This study examined the utility of HDL-associated single nucleotide polymorphisms (SNPs) for CVD risk prediction in European Americans with T2D enrolled in the Diabetes Heart Study (DHS).

METHODS - Genetic risk scores (GRS) of HDL-associated SNPs were constructed and evaluated for potential associations with mortality and with coronary artery calcified atherosclerotic plaque (CAC), a measure of subclinical CVD strongly associated with CVD events and mortality. Two sets of SNPs were used to construct GRS; while all SNPs were selected primarily for their impacts on HDL, one set of SNPs had pleiotropic effects on other lipid parameters, while the other set lacked effects on low-density lipoprotein cholesterol (LDL) or triglyceride concentrations.

RESULTS - The GRS were specifically associated with HDL concentrations (4.90 × 10(-7) < p < 0.02) in models adjusted for age, sex, and body mass index (BMI), but were not associated with LDL or triglycerides. Cox proportional hazards regression analysis suggested the HDL-associated GRS had no impact on risk of CVD-mortality (0.48 < p < 0.99) in models adjusted for other known CVD risk factors. However, associations between several of the GRS and CAC were observed (3.85 × 10(-4) < p < 0.03) in models adjusted for other known CVD risk factors.

CONCLUSIONS - The GRS analyzed in this study provide a tool for assessment of HDL-associated SNPs and their impact on CVD risk in T2D. The observed associations between several of the GRS and CAC suggest a potential role for HDL-associated SNPs on subclinical CVD risk in patients with T2D.

MeSH Terms (15)

Adult Aged Aged, 80 and over Cardiovascular Diseases Cholesterol, HDL Coronary Artery Disease Diabetes Mellitus, Type 2 Female Genetic Predisposition to Disease Humans Male Middle Aged Plaque, Atherosclerotic Polymorphism, Single Nucleotide Vascular Calcification

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