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Rs6922269 marker at the MTHFD1L gene predict cardiovascular mortality in males after acute coronary syndrome

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Abstract

Myocardial infarction (MI) is the leading cause of death in industrialized countries. All the traditional risk factors for MI are responsible for approximately 50 % of cases of MI cases. Attention therefore has recently focused on genetic variants that are not associated with conventional risk factors. One of them is the marker rs6922269, which has been suggested as a risk factor for development of MI in Western populations. We analyzed the relationship between rs6922269 variant on MTHFD1L gene and (i) risk of the acute coronary syndrome (ACS) in the Czech population and (ii) mortality in 7 years follow up. Rs6922269 (G>A) variant was analyzed (CR 99.3 % for patients and 98.0 % for controls) by PCR–RFLP in consecutively examined 1614 men and 503 women with ACS (age below 65 years) and in population-based controls––1191 men and 1368 women (aged up to 65 years). ANOVA and Chi square were used for statistical analysis. The genotype frequencies were almost identical (P = 0.87) in the ACS patients and in controls and no differences were observed, if males (P = 0.73) and females (P = 0.93) were analysed separately. In addition, rs6922269 polymorphism was not associated with the classical risk factors (dyslipidemia, hypertension, obesity, smoking, diabetes) in control population. Cardiovascular mortality was significantly higher in males, carriers of the AA genotype (P < 0.001, OR 2.52, 95 % CI 1.40–4.55, for AA vs. +G). We conclude, that rs6922269 variant at MTHFD1L gene could be an important prognostic factor for cardiovascular mortality in patients after ACS.

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References

  1. Hubacek JA, Stanek V, Gebauerova M, Pilipcincova A, Dlouha D, Poledne R et al (2010) A FTO variant and risk of acute coronary syndrome. Clin Chim Acta 411:1069–1072

    Article  CAS  PubMed  Google Scholar 

  2. Palomaki GE, Melillo S, Bradley LA (2010) Association between 9p21 genomic markers and heart disease: a meta-analysis. JAMA 303:648–656

    Article  CAS  PubMed  Google Scholar 

  3. Hubacek JA, Staněk V, Gebauerová M, Poledne R, Aschermann M, Skalicka H et al (2012) Association between a marker on chromosome 9 and acute coronary syndrome. Confirmatory study on Czech population. Folia Biol (Praha) 58:203–208

    CAS  Google Scholar 

  4. Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, Mayer B et al (2007) Genomewide association analysis of coronary artery disease. N Engl J Med 357:443–453

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Saade S, Cazier JB, Ghassibe-Sabbagh M, Youhanna S, Badro DA, Kamatani Y et al (2011) FGENTCARD consortium. Large scale association analysis identifies three susceptibility loci for coronary artery disease. PLoS One 6:e29427

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Angelakopoulou A, Shah T, Sofat R, Shah S, Berry DJ, Cooper J et al (2012) Comparative analysis of genome-wide association studies signals for lipids, diabetes, and coronary heart disease: Cardiovascular Biomarker Genetics Collaboration. Eur Heart J 33:393–407

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Ghazouani L, Khalifa SB, Abboud N, Perret C, Nicaud V, Ben Khalfallah A et al (2010) Association of three polymorphisms selected from a genome-wide association study with coronary heart disease in the Tunisian population. J Thromb Thrombolysis 29:114–118

    Article  CAS  PubMed  Google Scholar 

  8. Wang AZ, Li L, Zhang B, Shen GQ, Wang QK (2011) Association of SNP rs17465637 on chromosome 1q41 and rs599839 on 1p13.3 with myocardial infarction in an American caucasian population. Ann Hum Genet 75:475–482

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Hubacek JA, Staněk V, Gebauerová M, Pilipcincova A, Poledne R, Aschermann M et al (2010) Lack of an association between connexin-37, stromelysin-1, plasminogen activator-inhibitor type 1 and lymphotoxin-alpha genes and acute coronary syndrome in Czech Caucasians. Exp Clin Cardiol 15:e52–e56

    PubMed Central  CAS  PubMed  Google Scholar 

  10. Tunstall-Pedoe H, Kuulasmaa K, Tolonen H, Davidson M, Mendis S. MONICA monograph and multimedia sourcebook. (2003). Tunstal-Pedoe H, editor. Geneva: World Health Organisation. http://whqlibdoc.who.int/publication/2003/9241562234.pdf

  11. Palmer BR, Slow S, Ellis KL, Pilbrow AP, Skelton L, Frampton CM et al (2014) Genetic polymorphism rs6922269 in the MTHFD1L gene is associated with survival an baseline active vitamin B12 levels in post-acute coronary syndrome patients. PLos One 5:e89029

    Article  Google Scholar 

  12. Morgan TM, House J, Cresci S, Jones P, Allayee H, Hazen SL et al (2011) Investigation of 95 variants identified in a genome-wide study for association with mortality after acute coronary syndrome. BMC Med Genet 12:127

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Munafò MR (2009) Reliability and replicability of genetic association studies. Addiction 104:1439–1440

    Article  PubMed  Google Scholar 

  14. Hashad IM, Abdel Rahman MF, Abdel-Maksoud SM, Amr KS, Effat LK, Shaban GM et al (2014) C242T polymorphism of NADPHoxidase p22phox gene reduces the risk of coronary artery disease in a random sample of Egyptian population. Mol Biol Rep 41:2281–2286

    Article  CAS  PubMed  Google Scholar 

  15. Iqbal R, Jahan N, Sun Y, Xue H (2014) Genetic association of lipid metabolism related SNPs with myocardial infarction in the Pakistani population. Mol Biol Rep 41:1545–1552

    Article  CAS  PubMed  Google Scholar 

  16. Franceschini N, Carty C, Bůzková P, Reiner AP, Garrett T, Lin Y et al (2011) Association of genetic variants and incident coronary heart disease in multiethnic cohorts: the PAGE study. Circ Cardovasc Genet 4:661–672

    Article  CAS  Google Scholar 

  17. Cunnington MS, Mayosi BM, Hall DH, Avery PJ, Farrall M, Vickers MA et al (2009) Novel genetic variants linked to coronary artery disease by genome-wide association are not associated with carotid artery intima-media thickness or intermediate risk phenotypes. Atherosclerosis 203:41–44

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Muendlein A, Saely CH, Rhomberg S, Sonderegger G, Loacker S, Rein P et al (2009) Evaluation of the association of genetic variants on the chromosomal loci 9p21.3, 6q25.1, and 2q36.3 with angiographically characterized coronary artery disease. Atherosclerosis 205:174–180

    Article  CAS  PubMed  Google Scholar 

  19. Kooner JS, Chambers JC, Aguilar-Salinas CA, Hinds DA, Hyde CL, Warnes GR et al (2008) Genome-wide scan identifies variation in MLXIPL associated with plasma triglycerides. Nat Genet 40:149–151

    Article  CAS  PubMed  Google Scholar 

  20. Vrablik M, Ceska R, Adamkova V, Peasey A, Pikhart H, Kubinova R et al (2008) MLXIPL variant in individuals with low and high triglyceridemia in white population in Central Europe. Hum Genet 124:553–555

    Article  CAS  PubMed  Google Scholar 

  21. Bierut LJ, Madden PA, Breslau N, Johnson EO, Hatsukami D, Pomerleau OF et al (2007) Novel genes identified in a high-density genome wide association study for nicotine dependence. Hum Mol Genet 16:24–35

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Hubacek JA, Dlouha D, Lanska V, Adamkova V (2012) Lack of an association between three tagging SNPs within the FTO gene and smoking behavior. Nicotine Tob Res 14:998–1002

    Article  CAS  PubMed  Google Scholar 

  23. Nelis M, Esko T, Mägi R, Zimprich F, Zimprich A, Toncheva D et al (2009) Genetic structure of Europeans: a view from the North-East. PLoS One 4:e5472

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by project NT12217-5 (Internal Grant Agency, Ministry of Health, Czech Republic) and by the project (Ministry of Health, Czech Republic) for the development of research organisation 00023001 (IKEM, Prague, Czech Republic)––Institutional support.

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Authors and Affiliations

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

    J. A. Hubacek, R. Poledne & J. Piťha

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

    V. Staněk, M. Gebauerová & H. Hrabáková

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

    M. Aschermann & H. Skalická

  4. Department of Cardiology, Homolka Hospital, Prague, Czech Republic

    J. Matoušková & A. Kruger

  5. Department of Cardiology, Cardiocenter, University Hospital Královské Vinohrady, Prague, Czech Republic

    M. Pěnička & H. Hrabáková

  6. Department of Cardiology, 2nd Medical School, University Hospital Motol, Charles University, Prague, Czech Republic

    J. Veselka & P. Hájek

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

    V. Lánská

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

    V. Adámková

  9. IKEM-DEM-LMG, Videnska 1958/9, 140 21, Prague 4, Czech Republic

    J. A. Hubacek

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  1. J. A. Hubacek
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  2. V. Staněk
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Correspondence to J. A. Hubacek.

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Hubacek, J.A., Staněk, V., Gebauerová, M. et al. Rs6922269 marker at the MTHFD1L gene predict cardiovascular mortality in males after acute coronary syndrome. Mol Biol Rep 42, 1289–1293 (2015). https://doi.org/10.1007/s11033-015-3870-1

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  • DOI: https://doi.org/10.1007/s11033-015-3870-1

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