Genetically elevated apolipoprotein A-I, high-density lipoprotein cholesterol levels, and risk of ischemic heart disease

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Abstract

Context: Epidemiologically, levels of high-density lipoprotein (HDL) cholesterol and its major protein constituent, apolipoprotein A-I (apoA-I), are inversely related to risk of ischemic heart disease (IHD). Objective: We tested whether common genetic variation in the apolipoprotein A1 gene (APOA1) contributes to apoA-I and HDL cholesterol levels and risk of IHD in the general population. Design: We resequenced the regulatory and coding regions of APOA1 in 190 individuals from the Copenhagen City Heart Study with the lowest 1% (n = 95) and highest 1% (n = 95) apoA-I levels. Two single-nucleotide polymorphisms (SNPs) were subsequently genotyped in the Copenhagen City Heart Study (n = 10,273) and in 2361 cases with IHD (the Copenhagen Ischemic Heart Disease Study). Results: In total, 13 genetic variants were identified. Three SNPs, g.-560A→C, g.-151C→T, and *181A→G, determined a haplotype that differed between high and low apoA-I groups (6 vs. 1%, P = 0.002). Genotype combinations of two SNPs, the g.-560A→C (tagging the g.-560A→C/ g.-151C→T/*181A→G haplotype) and g.-310G→A (situated near a potential functional promoter site), were associated with increases in apoA-I and HDL cholesterol levels of up to 6.6 and 8.5%, respectively, resulting in theoretically predicted reductions in risk of 9 and 8% for IHD and 14 and 12% for myocardial infarction (MI). Despite this, these same genotype combinations were not associated with decreased risk of IHD or MI. Conclusion: Common genetic variation in APOA1 associated with increased apoA-I and HDL cholesterol levels did not associate with decreased risk of IHD or MI. Copyright © 2010 by The Endocrine Society.

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APA

Haase, C. L., Tybjærg-Hansen, A., Grande, P., & Frikke-Schmidt, R. (2010). Genetically elevated apolipoprotein A-I, high-density lipoprotein cholesterol levels, and risk of ischemic heart disease. Journal of Clinical Endocrinology and Metabolism, 95(12). https://doi.org/10.1210/jc.2010-0450

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