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

Show full item record



Permalink

http://hdl.handle.net/10138/160557

Citation

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 organization: Institute for Molecular Medicine Finland
Children's Hospital
Clinicum
Medicum
Marja-Liisa Lokki / Principal Investigator
Transplantation Laboratory
Aarno Palotie / Principal Investigator
Department of Medicine
Kardiologian yksikkö
Biostatistics Helsinki
Quantitative Genetics
Complex Disease Genetics
Genomics of Neurological and Neuropsychiatric Disorders
Statistical and population genetics
Date: 2015-10-28
Language: eng
Number of pages: 16
Belongs to series: PLoS One
ISSN: 1932-6203
DOI: https://doi.org/10.1371/journal.pone.0140576
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
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


Files in this item

Total number of downloads: Loading...

Files Size Format View
journal.pone.0140576.PDF 1.662Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record