Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
Scopus CiteScore – 3.4 (CiteScore Tracker 3.7)
Index Copernicus  – 161.11; MNiSW – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2017, vol. 26, nr 8, November, p. 1213–1217

doi: 10.17219/acem/67460

Publication type: original article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

MRAS gene marker rs9818870 is not associated with acute coronary syndrome in the Czech population and does not predict mortality in males after acute coronary syndrome

Jaroslav A. Hubacek1,A,C,D,F, Vladimir Stanek2,A,B,E, Marie Gebauerova2,A,B,E, Richard Ceska3,A,B,E, Vera Adamkova4,A,B,E, Vera Lanska5,A,C,E, Jan Pitha1,A,B,C,D,F

1 Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

2 Cardiology Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

3 2nd Department of Internal Medicine, General University Hospital, Prague, Czech Republic

4 Preventive Cardiology Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

5 Statistical Unit, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

Abstract

Background. Genome-wide association studies (GWAs) focused on cardiovascular diseases reveal variants within genes which have not been analyzed through the pre-GWAs era, and whose function is often unknown. One of them is variant rs9818870 at the MRAS gene locus.
Objectives. To analyze if MRAS polymorphism is associated with acute coronary syndrome (ACS) risk in a Czech population and with mortality in male patients after myocardial infarction.
Material and Methods. 1,779 male patients with ACS (aged 55.3 ±7.9 years) and 673 female patients with ACS (aged 64.0 ±8.1 years) were genotyped for rs9818870 polymorphism using the PCR-RFLP method. In a subset of 1,221 patients, detailed diagnoses (901 subjects with STEMI, 280 subjects with NSTEMI, 40 cases with unstable angina pectoris) were recorded. In 1,614 males, records about total and cardiovascular mortality were available.
Results. Whether the entire populations or males and females have been analyzed separately or not, we have not confirmed the described association between DNA marker rs9818870 and ACS in Czechs (30.4% vs 29.4% carriers of the minor T allele [recessive model], p = 0.54; OR 1.05; 95% CI 0.89–1.24 for males and 32.1% vs 29.7% carriers of the minor T allele, p = 0.28; OR 1.12; 95% CI 0.91–1.37 for females). Types of the ACS (STEMI and NSTEMI) or mortality (in males only) were not associated with the analyzed polymorphism (all p > 0.34).
Conclusion. The rs9818870 variant is not associated with ACS or mortality in ACS patients in the Czech Slavonic population.

Key words

polymorphism, myocardial infarction, mortality, MRAS, Slavs

References (25)

  1. Kessler T, Schunkert H. Clinical validation of genetic markers for improved risk estimation. Eur J Prev Cardiol. 2012;19(2)(Suppl):25–32.
  2. Liu C, Mou S, Pan C. The FTO gene rs9939609 polymorphism predicts risk of cardiovascular disease: A systematic review and meta-analysis. PLoS One. 2013;8:e71901.
  3. Gustavsson J, Mehlig K, Leander K, et al. FTO genotype, physical activity, and coronary heart disease risk in Swedish men and women. Circ Cardiovasc Genet. 2014;7:171–177.
  4. Hamsten A, Eriksson P. Quest for genes and mechanisms linking the human chromosome 9p21.3 locus to cardiovascular disease. Circulation. 2012;126:1815–1817.
  5. Roberts R, Stewart AF. 9p21 and the genetic revolution for coronary artery disease. Clin Chem. 2012;58:104–112.
  6. Kerkhoff E, Rapp UR. The Ras-Raf relationship: An unfinished puzzle. Adv Enzyme Regul. 2001;41:261–267.
  7. Galkina E, Ley K. Vascular adhesion molecules in atherosclerosis. Arterioscler Thromb Vasc Biol. 2007;27:2292–2301.
  8. Erdmann J, Grosshennig A, Braund PS, et al. New susceptibility locus for coronary artery disease on chromosome 3q22.3. Nat Genet. 2009;41:280–282.
  9. O'Donnell CJ, Kavousi M, Smith AV, et al. Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction. Circulation. 2011;124:2855–2864.
  10. Ellis KL, Frampton CM, Pilbrow AP, et al. Genomic risk variants at 1p13.3, 1q41, and 3q22.3 are associated with subsequent cardiovascular outcomes in healthy controls and in established coronary artery disease. Circ Cardiovasc Genet. 2011;4:636–646.
  11. Alshahid M, Wakil SM, Al-Najai M, et al. New susceptibility locus for obesity and dyslipidaemia on chromosome 3q22.3. Hum Genomics. 2013;7:15.
  12. Hubacek JA, Vrablik M, Dlouha D, et al. Gene variants at FTO, 9p21, and 2q36.3 are age-independently associated with myocardial infarction in Czech men. Clin Chim Acta. 2016;454:119–123.
  13. Hubacek JA, Staněk V, Gebauerová M, et al. Association between a marker on chromosome 9 and acute coronary syndrome: Confirmatory study on Czech population. Folia Biol (Praha). 2012;58:203–208.
  14. Hubacek JA, Staněk V, Gebauerová M, et al. Rs6922269 marker at the MTHFD1L gene predict cardiovascular mortality in males after acute coronary syndrome. Mol Biol Rep. 2015;42:1289–1293.
  15. Tunstall-Pedoe H, Kuulasmaa K, Tolonen H, Davidson M, Mendis S. MONICA monograph and multimedia sourcebook. World's largest study of heart disease, stroke, risk factors, and population trends 1979–2002. Geneva: World Health Organisation, 2003.
  16. Hubacek JA, Lanska V, Adamkova V. Lack of an association between SNPs within the cholinergic receptor genes and smoking behavior in a Czech post-MONICA study. Genet Mol Biol. 2014;37:625–630.
  17. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for DNA extraction from human nucleated cells. Nucleic Acid Res. 1988;16:1215.
  18. Day IN, Humphries SE, Richards S, Norton D, Reid M. High-throughput genotyping using horizontal polyacrylamide gels with wells arranged for microplate array diagonal gel electrophoresis (MADGE). Biotechniques. 1995;19:830–835.
  19. Hubáček JA, Pikhart H, Peasey A, Kubínová R, Bobák M. Nobody is perfect: Comparison of the accuracy of PCR-RFLP and KASP™ method for genotyping. ADH1B and FTO polymorphisms as examples. Folia Biol (Praha). 2015;61:156–160.
  20. Palomaki GE, Melillo S, Bradley LA. Association between 9p21 genomic markers and heart disease: A meta-analysis. JAMA. 2010;303:648–656.
  21. Munir MS, Wang Z, Alahdab F, et al. The association of 9p21–3 locus with coronary atherosclerosis: A systematic review and meta-analysis. BMC Med Genet. 2014;15:66.
  22. Calkin AC, Tontonoz P. Genome-wide association studies identify new targets in cardiovascular disease. Sci Transl Med. 2010;2:48ps46.
  23. Davignon J, Dubuc G, Seidah NG. The influence of PCSK9 polymorphisms on serum low-density lipoprotein cholesterol and risk of atherosclerosis. Curr Atheroscler Rep. 2010;12:308–315.
  24. Haas U, Sczakiel G, Laufer SD. MicroRNA-mediated regulation of gene expression is affected by disease-associated SNPs within the 3'-UTR via altered RNA structure. RNA Biol. 2012;9:924–937.
  25. van Rooij E, Sutherland LB, Liu N, et al. A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proc Natl Acad Sci USA. 2006;103:18255–18260.