Indian Journal of Clinical Biochemistry

, Volume 24, Issue 2, pp 137–141 | Cite as

MTHFR (Ala 222 Val) polymorphism and AMI in patients with type II diabetes mellitus

  • T. Angeline
  • G. Thiruvarutselvi
  • W. Isabel
  • Rita Mary Aruna
  • Rama Devi
  • Nirmala Jeyaraj
Article
First Online:

Abstract

The prevalent Ala222Val single nucleotide polymorphism of the MTHFR gene has been shown to be associated with type II diabetes. The objective of the present study was to find out whether there is genetic predisposition for development of acute myocardial infarction in type II diabetes mellitus among South Indian Tamil population. PCR-based restriction enzyme analysis was performed in DNA isolated from 120 acute myocardial infarction patients with diabetes mellitus and 100 non diabetic healthy individuals with no documented cardiovascular diseases. The results indicate that the MTHFR 677TT genotype is absent in both case and controls. The MTHFR 677CT genotype was observed among 32 (26.7 %) cases and 20 (20%) controls and the MTHFR 677CC genotype among 88 (73.3%) cases and 80 (80%) controls. The allelic frequencies were in accordance to Hardy Weinberg equilibrium. There was no statistical difference in genotype distribution between cases and controls. In conclusion, we suggest that the analysis of MTHFR genotyping for C677T polymorphism alone need not be considered to find out whether there is genetic predisposition for development of acute myocardial infarction in type II diabetes mellitus among South Indian Tamil population.

Key Words

MTHFR gene Type II diabetes Polymorphism Genetic predisposition Acute Myocardial Infarction 
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References

  1. 1.
    Audelin MC, Genest J. Homocysteine and cardiovascular disease in diabetes mellitus. Atherosclerosis 2001; 159: 497–511.PubMedCrossRefGoogle Scholar
  2. 2.
    Ozmen B, Ozmen D, Turgan N, Habif S, Mutaf I, Bayindir O. Association between homocysteinemia and renal function in patients with type 2 diabetes mellitus. Ann Clin Lab Sci 2002; 32(3):279–286.PubMedGoogle Scholar
  3. 3.
    Chico A, Perez A, Cordoba A, Arcelus R, Carreras G, de Leiva A, Gonzalez-Sastre F, Blanco-Vaca F. Plasma homocysteine is related to albumin excretion rate in patients with diabetes mellitus: a new link between diabetic nephropathy and cardiovascular disease. Diabetologia 1998;41: 684–693.PubMedCrossRefGoogle Scholar
  4. 4.
    Hoogeveen EK, Kostense PJ, Beks PJ, Mackaay AJ, Jakobs C, Bouter LM, Heine RJ, Stehouwer CD. Hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, especially in non-insulin dependent diabetes mellitus: a population-based study. Arterioscler Thromb Vasc Biol 1998; 18: 133–138.PubMedGoogle Scholar
  5. 5.
    Angeline T, Rita Mary Aruna, Ramadevi K, Mohan G, Nirmala J. Homocysteine status and acute myocardial infarction among Tamilians. Ind J Clin Biochem 2005; 20(1):18–20.CrossRefGoogle Scholar
  6. 6.
    Angeline T, Nirmala J, Tsongalis GJ. MTHFR Gene polymorphisms, B-vitamins and hyperhomocystinemia in young and middle-aged acute myocardial infarction patients. Exp Mol Pathol 2007; 227–233.Google Scholar
  7. 7.
    Spotila LD, Jacques PF, Berger PB, Ballman KV, Ellison RC, Rozen R. Age dependence of the influence of Methylene tetrahydrofolate reductase genotype on plasma homocysteine level. Am J Epidemiol 2003; 158: 871–877.PubMedCrossRefGoogle Scholar
  8. 8.
    Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJ, den Heijer M, Kluijtmans LA, van den Heuvel LP. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995; 10:111–113.PubMedCrossRefGoogle Scholar
  9. 9.
    Friedman G, Goldschmidt N, Friedlander Y, Ben-Yehuda A, Selhub J, Babaey S, Mendel M, Kidron M, Bar-On H. A common mutation A1298C in human methylenetetrahydrofolate reductase gene, Association with plasma total homocysteine and folate concentrations. Am Soc Nutr Sci 1999; 129:1656–1661.Google Scholar
  10. 10.
    Crott JW, Mashiyama ST, Ames BN, Fenech MF. Methylenetetrahydrofolate reductase C677T polymorphism does not alter folic acid deficiency-induced Uracil incorporation into primary human lymphocyte DNA in vitro Cancer. Epidemiol Biomarkers Prev 2001; 22: 1019–1025.Google Scholar
  11. 11.
    Kluijtmans LA, van den Heuvel LP, Boers GH, Frosst P, Stevens EM, van Oost BA, et al. Molecular genetic analysis in mild hyperhomocysteinemia: a common mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease. Am J Hum Genet 1996; 58: 35–41.PubMedGoogle Scholar
  12. 12.
    Morita H, Taguchi J, Kurihara H, Kitaoka M, Kaneda H, Kurihara Y, et al. Genetic polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) as a risk factor for coronary artery disease. Circulation 1997; 95: 2032–2036.PubMedGoogle Scholar
  13. 13.
    Neugebauer S, Baba T, Watanabe T. Defective homocysteine metabolism as a risk factor for diabetic retinopathy. Lancet 1997; 349: 473–474.PubMedCrossRefGoogle Scholar
  14. 14.
    Sambrook J, Russell DW. Molecular cloning, A laboratory manual, 3rd ed. Cold Spring Harbor Laboratory 2001; 5.1–5.86.Google Scholar
  15. 15.
    Angeline T, Nirmala J, Granito S, Tsongalis GJ. Prevalence of MTHFR gene polymorphisms (C677T and A1298C) among Tamilians. Exp Mol Pathol 2004;77(2):85–88.PubMedCrossRefGoogle Scholar
  16. 16.
    Dekov V, Whincup P, Papacosta O, Ebrahim S, Lennon L, Ueland PM, Refsum H, Humphries SE, Gudnason V. The effect of the C677T and A1298C polymorphism in the Methylene tetrahydrofolate reductase gene on homocysteine levels in elderly men and women from the British Regional Heart study. Atherosclerosis 2001; 154: 659–666.CrossRefGoogle Scholar
  17. 17.
    Robien K, Ulrich CM. 5,10-Methylenetetrahydrofolate reductase polymorphisms and leukemia risk: A Human Genome Epidemology Review minireview. Am J Epidemiol 2003; 157: 571–582.PubMedCrossRefGoogle Scholar
  18. 18.
    Zetterberg H, Regland B, Palmér M, Ricksten A, Palmqvist L, Rymo L, Arvanitis DA, Spandidos DA, Blennow K. Increased frequency of combined methylenetetrahydrofolate reductase C677T and A1298C mutated alleles in spontaneously aborted embryos. Eur J Hum Genet 2002; 10: 113–118.PubMedCrossRefGoogle Scholar
  19. 19.
    Devi RR, Govindaiah V, Ramakrishna G, Naushad SM. Prevalence of methylene tetrahydrofolate reductase polymorphism in South Indian population. Curr Sci 2004; 89(3): 440–443.Google Scholar
  20. 20.
    Isotalo PA, Wells GA. Donnelly JG. Neonatal and fetal methylenetetrahydrofolate reductase genetic polymorphisms, An examination of C677T and A1298C mutations. Am J Hum Genet 2000; 67:986–990.PubMedCrossRefGoogle Scholar
  21. 21.
    Maeda M, Yamamoto I, Fukuda M, Nishida M, Fujitsu J, Nonen S, et al. MTHFR Gene Polymorphism as a Risk Factor for Diabetic Retinopathy in Type 2 Diabetic Patients without Serum Creatinine Elevation. Diabetes Care 2003; 26: 547–548.PubMedCrossRefGoogle Scholar
  22. 22.
    Ksiazek P, Bednarek-Skublewska A, Buraczynska M. The C677T methylenetetrahydrofolate reductase gene mutation and nephropathy in type 2 diabetes mellitus. Med Sci Monit 2004; 10(2): BR47–BR51.PubMedGoogle Scholar
  23. 23.
    Yilmaz H, Agachan B, Ergen A, Karaalib ZE, Isbir T. Methylene tetrahydrofolate reductase C677T mutation and left ventricular hypertrophy in Turkish patients with type II diabetes mellitus. J Biochem Mol Biol 2004; 37(2):234–238.PubMedGoogle Scholar
  24. 24.
    Agullo-Ortuno MT, Albaladejo MD, Parra S, Rodriguez-Manotas M, Fenollar M, Ruiz-Espejo F, Tebar J, Martinez P. Plasmatic homocysteine concentration and its relationship with complications associated to diabetes mellitus. Clin Chim Acta 2002; 326:105–112.PubMedCrossRefGoogle Scholar
  25. 25.
    Shpichinetsky V, Raz I, Friedlander Y, Goldschmidt N, Wexler ID, Ben-Yehuda A, Friedman G. The association between two common mutations C677T and A1298C in human methylenetetrahydrofolate reductase gene and the risk for diabetic nephropathy in type II diabetic patients. J Nutr 2000; 130(10):2493–2497.PubMedGoogle Scholar
  26. 26.
    Sun J, Xu Y, Zhu Y, Lu H. Genetic polymorphism of methylenetetrahydrofolate reductase as a risk factor for diabetic nephropathy in Chinese type 2 diabetic patients. Diabetes Res Clin Pract 2004; 64(3):185–190.PubMedCrossRefGoogle Scholar

Copyright information

© Association of Clinical Biochemists of India 2009

Authors and Affiliations

  • T. Angeline
    • 1
  • G. Thiruvarutselvi
    • 1
  • W. Isabel
    • 1
  • Rita Mary Aruna
    • 2
  • Rama Devi
    • 3
  • Nirmala Jeyaraj
    • 1
  1. 1.PG & Research Department of Zoology & BiotechnologyLady Doak CollegeMaduraiIndia
  2. 2.Penang International Dental CollegeSalemIndia
  3. 3.Institute of BiochemistryMadras Medical CollegeChennaiIndia

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