Journal Article

Genetic Variants on Chromosome 1p13.3 Are Associated with Non-ST Elevation Myocardial Infarction and the Expression of DRAM2 in the Finnish Population

Salo, Perttu P., Sarin, Antti-Pekka, Karhunen, Pekka J., Pirinen, Matti, Lokki, Marja-Liisa, Nikus, Kjell, Ripatti, Samuli, Palotie, Aarno, Eskola, Markku, Nieminen, Markku S., Havulinna, Aki S., Sinisalo, Juha, Kettunen, Johannes, Perola, Markus, Huikuri, Heikki, Salomaa, Veikko, Vaara, Satu

2015

Overview

Myocardial infarction (MI) is divided into either ST elevation MI (STEMI) or non-ST elevation MI (NSTEMI), differing in a number of clinical characteristics. We sought to identify genetic variants conferring risk to NSTEMI or STEMI by conducting a genome-wide association study (GWAS) of MI stratified into NSTEMI and STEMI in a consecutive sample of 1,579 acute MI cases with 1,576 controls. Subsequently, we followed the results in an independent population-based sample of 562 cases and 566 controls, a partially independent prospective cohort (N = 16,627 with 163 incident NSTEMI cases), and examined the effect of disease-associated variants on gene expression in 513 healthy participants. Genetic variants on chromosome 1p13.3 near the damage-regulated autophagy modulator 2 gene DRAM2 associated with NSTEMI (rs656843; odds ratio 1.57, P = 3.11 × 10(-10)) in the case-control analysis with a consistent but not statistically significant effect in the prospective cohort (rs656843; hazard ratio 1.13, P = 0.43). These variants were not associated with STEMI (rs656843; odds ratio, 1.11, P = 0.20; hazard ratio 0.97, P = 0.87), appearing to have a pronounced effect on NSTEMI risk. A majority of the variants at 1p13.3 associated with NSTEMI were also associated with the expression level of DRAM2 in blood leukocytes of healthy controls (top-ranked variant rs325927, P = 1.50 × 10(-12)). The results suggest that genetic factors may in part influence whether coronary artery disease results in NSTEMI rather than STEMI.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acute coronary syndromes / Aged / Autophagy / Biomarkers / Cardiology / Cardiovascular disease / Cell cycle / Cell death / Chromosome 1 / Chromosomes / Chromosomes, Human, Pair 1 - genetics / Consortia / Coronary artery / Coronary artery disease / Coronary vessels / Female / Finland / Gene expression / Gene Expression Regulation / Genetic aspects / Genetic Association Studies / Genetic diversity / Genetic factors / Genetic Loci / Genetic Predisposition to Disease / Genetic variance / Genetic Variation / Genome-wide association studies / Genome-Wide Association Study / Genomes / Genomics / Health aspects / Health risk assessment / Heart attack / Heart attacks / Heart diseases / Hospitals / Humans / Laboratories / Leukocytes / Linkage Disequilibrium - genetics / Male / Medical diagnosis / Medicine / Membrane Proteins - genetics / Membrane Proteins - metabolism / Meta-analysis / Middle Aged / Myocardial infarction / Myocardial Infarction - genetics / Phagocytosis / Phenotype / Polymorphism, Single Nucleotide - genetics / Principal components analysis / Reproducibility of Results / Risk Factors / Statistical analysis / Studies / Task forces