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; 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; Salomaa, Veikko; Palotie, Aarno; Nieminen, Markku S; Sinisalo, Juha; Perola, Markus (2015)
Karhunen, Pekka J
Nieminen, Markku S
Plos ONE 10 10
This publication is copyrighted. You may download, display and print it for Your own personal use. Commercial use is prohibited.
Julkaisun pysyvä osoite on
Public Library of Science open access
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.
- Artikkelit