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

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Salo , P P , Vaara , S , Kettunen , J , Pirinen , M , Sarin , A-P , Huikuri , H , Karhunen , P J , Eskola , M , Nikus , K , Lokki , M-L , Ripatti , S , Havulinna , A S , Salomaa , V , Palotie , A , Nieminen , M S , Sinisalo , J & Perola , M 2015 , ' Genetic Variants on Chromosome 1p13.3 Are Associated with Non-ST Elevation Myocardial Infarction and the Expression of DRAM2 in the Finnish Population ' , PLoS One , vol. 10 , no. 10 , 0140576 . https://doi.org/10.1371/journal.pone.0140576

Title: Genetic Variants on Chromosome 1p13.3 Are Associated with Non-ST Elevation Myocardial Infarction and the Expression of DRAM2 in the Finnish Population
Author: Salo, Perttu P.; Vaara, Satu; Kettunen, Johannes; Pirinen, Matti; Sarin, Antti-Pekka; Huikuri, Heikki; Karhunen, Pekka J.; Eskola, Markku; Nikus, Kjell; Lokki, Marja-Liisa; Ripatti, Samuli; Havulinna, Aki S.; Salomaa, Veikko; Palotie, Aarno; Nieminen, Markku S.; Sinisalo, Juha; Perola, Markus
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Medicum
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Department of Medicine
University of Helsinki, Clinicum
University of Helsinki, Institute for Molecular Medicine Finland
Date: 2015-10-28
Language: eng
Number of pages: 16
Belongs to series: PLoS One
ISSN: 1932-6203
URI: http://hdl.handle.net/10138/160557
Abstract: 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 x 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 x 10(-12)). The results suggest that genetic factors may in part influence whether coronary artery disease results in NSTEMI rather than STEMI.
Subject: GENOME-WIDE ASSOCIATION
ACUTE CORONARY SYNDROMES
UNIVERSAL DEFINITION
GENOTYPE IMPUTATION
ARTERY-DISEASE
AUTOPHAGY
RISK
COHORT
LOCI
SUSCEPTIBILITY
3111 Biomedicine
3121 General medicine, internal medicine and other clinical medicine
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