Genetic Variants on Chromosome 1p13.3 Are Associated with Non-ST Elevation Myocardial Infarction and the Expression of DRAM2 in the Finnish Population.
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 stratifie...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4625034?pdf=render |
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| author | Perttu P Salo Satu Vaara Johannes Kettunen Matti Pirinen Antti-Pekka Sarin Heikki Huikuri Pekka J Karhunen Markku Eskola Kjell Nikus Marja-Liisa Lokki Samuli Ripatti Aki S Havulinna Veikko Salomaa Aarno Palotie Markku S Nieminen Juha Sinisalo Markus Perola |
| author_facet | Perttu P Salo Satu Vaara Johannes Kettunen Matti Pirinen Antti-Pekka Sarin Heikki Huikuri Pekka J Karhunen Markku Eskola Kjell Nikus Marja-Liisa Lokki Samuli Ripatti Aki S Havulinna Veikko Salomaa Aarno Palotie Markku S Nieminen Juha Sinisalo Markus Perola |
| author_sort | Perttu P Salo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T03:03:22Z |
| format | Article |
| id | doaj.art-a4f735f8e042438e81cc55fc4938f2ae |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T03:03:22Z |
| publishDate | 2015-01-01 |
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| spelling | doaj.art-a4f735f8e042438e81cc55fc4938f2ae2022-12-22T03:05:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011010e014057610.1371/journal.pone.0140576Genetic Variants on Chromosome 1p13.3 Are Associated with Non-ST Elevation Myocardial Infarction and the Expression of DRAM2 in the Finnish Population.Perttu P SaloSatu VaaraJohannes KettunenMatti PirinenAntti-Pekka SarinHeikki HuikuriPekka J KarhunenMarkku EskolaKjell NikusMarja-Liisa LokkiSamuli RipattiAki S HavulinnaVeikko SalomaaAarno PalotieMarkku S NieminenJuha SinisaloMarkus PerolaMyocardial 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.http://europepmc.org/articles/PMC4625034?pdf=render |
| spellingShingle | Perttu P Salo Satu Vaara Johannes Kettunen Matti Pirinen Antti-Pekka Sarin Heikki Huikuri Pekka J Karhunen Markku Eskola Kjell Nikus Marja-Liisa Lokki Samuli Ripatti Aki S Havulinna Veikko Salomaa Aarno Palotie Markku S Nieminen Juha Sinisalo Markus Perola 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 |
| title | Genetic Variants on Chromosome 1p13.3 Are Associated with Non-ST Elevation Myocardial Infarction and the Expression of DRAM2 in the Finnish Population. |
| title_full | Genetic Variants on Chromosome 1p13.3 Are Associated with Non-ST Elevation Myocardial Infarction and the Expression of DRAM2 in the Finnish Population. |
| title_fullStr | Genetic Variants on Chromosome 1p13.3 Are Associated with Non-ST Elevation Myocardial Infarction and the Expression of DRAM2 in the Finnish Population. |
| title_full_unstemmed | Genetic Variants on Chromosome 1p13.3 Are Associated with Non-ST Elevation Myocardial Infarction and the Expression of DRAM2 in the Finnish Population. |
| title_short | Genetic Variants on Chromosome 1p13.3 Are Associated with Non-ST Elevation Myocardial Infarction and the Expression of DRAM2 in the Finnish Population. |
| title_sort | genetic variants on chromosome 1p13 3 are associated with non st elevation myocardial infarction and the expression of dram2 in the finnish population |
| url | http://europepmc.org/articles/PMC4625034?pdf=render |
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