Christiane L Haase1, Anne Tybjærg-Hansen, Peer Grande, Ruth Frikke-Schmidt. 1. Department of Clinical Biochemistry Rigshospitalet, The Copenhagen City Heart Study, Bispebjerg University Hospital, and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
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.
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.
Authors: Lisanne L Blauw; Raymond Noordam; Sebastian Soidinsalo; C Alexander Blauw; Ruifang Li-Gao; Renée de Mutsert; Jimmy F P Berbée; Yanan Wang; Diana van Heemst; Frits R Rosendaal; J Wouter Jukema; Dennis O Mook-Kanamori; Peter Würtz; Ko Willems van Dijk; Patrick C N Rensen Journal: Eur J Hum Genet Date: 2018-11-12 Impact factor: 4.246
Authors: Haitham M Ahmed; Michael Miller; Khurram Nasir; John W McEvoy; David Herrington; Roger S Blumenthal; Michael J Blaha Journal: Am J Epidemiol Date: 2016-04-18 Impact factor: 4.897