Download PDF
Thromb Haemost 1998; 79(04): 727-730
DOI: 10.1055/s-0037-1615053
Rapid Communication
Schattauer GmbH

The High Prevalence of Thermolabile 5-10 Methylenetetrahydrofolate Reductase (MTHFR) in Italians Is not Associated to an Increased Risk for Coronary Artery Disease (CAD)

Rosanna Abbate
1   From the Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Florence
,
Iacopo Sardi
1   From the Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Florence
3   From the Dipartimento di Fisiopatologia Clinica, Unità di Genetica Medica, University of Florence, Florence, Italy
,
Guglielmina Pepe
1   From the Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Florence
2   From the Dipartimento di Biologia, University of Rome ‘Tor Vergata’, Rome
,
Rossella Marcucci
1   From the Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Florence
,
Tamara Brunelli
1   From the Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Florence
,
Domenico Prisco
1   From the Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Florence
,
Cinzia Fatini
3   From the Dipartimento di Fisiopatologia Clinica, Unità di Genetica Medica, University of Florence, Florence, Italy
,
Monia Capanni
1   From the Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Florence
,
Ignazio Simonetti
1   From the Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Florence
,
Gian Franco Gensini
1   From the Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Florence
› Author Affiliations
Further Information

Publication History

Received 08 August 1997

Accepted after revision 21 November 1997

Publication Date:
07 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

Mild hyperhomocysteinemia was found to be related to venous thrombosis, cerebrovascular and coronary artery disease (CAD). Some recent studies suggested that a mutation in the gene encoding for 5-10 methylenetetrahydrofolate reductase (MTHFR), due to a transition C→ at nucleotide 677, is a genetic risk factor for vascular disease. However, several further studies could not confirm this association.

We investigated 84 patients with CAD who underwent percutaneous transluminal coronary angioplasty (PTCA) and 106 healthy subjects.

The prevalence of the mutated homozygous genotype was much higher than in other Italian populations, Europeans or other major human groups, but no excess of the Val/Val homozygotes was found in patients (28.5%) with respect to healthy subjects (30.2%). Mutated homozygous MTHFR genotype (+/+) was not found to be related to the clinical manifestations of CAD, to the prevalence of the common risk factors and to the rate of restenosis.

In conclusion, thermolabile MTHFR does not appear to be associated “per se” with the risk for CAD or for restenosis after PTCA. The high frequency of the +/+ genotype in our Italian population (from Tuscany) confirms a wide macroheterogeneity and suggests a microheterogeneity in the genotype frequencies of the different ethnic populations.

Preliminary data of this paper were selected for an Oral Communication at the XVIth ISTH Congress.

 

  • References

  • 1 Boushey CJ, Beresford SSA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocyst(e)ine as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. JAMA 1995; 274: 1049-57.
    CrossrefPubMedSearch in Google Scholar
  • 2 Graham M. The European Concerted Action Project. Plasma homocysteine as a risk factor for vascular disease. JAMA 1997; 277: 1775-89.
    CrossrefPubMedSearch in Google Scholar
  • 3 Kang SS, Wong PWK, Susmano A, Sora J, Norusis M, Ruggie N. Thermolabile methylenetetrahydrofolate reductase: an inherited risk factor for coronary artery disease. Am J Hum Genet 1991; 48: 536-45.
    PubMedSearch in Google Scholar
  • 4 Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews R, Boers GJH, van den Heuvel L, Rosen R. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995; 10: 111-3.
    CrossrefPubMedSearch in Google Scholar
  • 5 Kang SS, Passen EL, Ruggie N, Wong PWK, Sora J. Thermolabile defect of methylenetetrahydrofolate reductase in coronary artery disease. Circulation 1993; 88: 1463-9.
    CrossrefPubMedSearch in Google Scholar
  • 6 Engbersen AMT, Franken DG, Boers GHJ, Stevens EMB, Trijbels FJM, Blom HJ. Thermolabile 5,10-methylenetetrahydrofolate reductase as a cause of mild hyperhomocysteinemia. Am J Hum Genet 1995; 56: 142-50.
    PubMedSearch in Google Scholar
  • 7 Arruda VR, von Zuben PM, Chiaparini LC, Annichino-Bizzacchi JM, Costa FF. The Mutation Ala677→Val in the methylene tetrahydrofolate reductase gene: a risk factor for arterial disease and venous thrombosis. Thromb Haemost 1997; 77: 818-21.
    Thieme ConnectPubMedSearch in Google Scholar
  • 8 Morita H, Taguchi J, Kurihara H, Kitaoka M, Kaneda H, Kurihara Y, Maemura K, Shindo T, Minamino T, Ohno M, Yamaoki K, Ogasawara K, Aizawa T, Suzuki S, Yazaki Y. Genetic polymorphism of 5,10-methylentetrahydrofolate reductase (MTHFR) as a risk factor for coronary artery disease. Circulation 1997; 95: 2032-6.
    CrossrefPubMedSearch in Google Scholar
  • 9 Kluijtmans LAJ, van den Heuvel LPWJ, Boers GHJ, Frosst P, Stevens EMB, van Oost BA, den Heijer M, Trijbels FJH, Rozen R, Blom H. Molecular genetic analysis in mild hyperhomocysteinemia: a common mutation in the methylentetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease. Am J Hum Genet 1996; 58: 35-41.
    PubMedSearch in Google Scholar
  • 10 Wilcken DEL, Wang XL, Sim AS, McCredie M. Distribution in healthy and coronary populations of the methylentetrahydrofolate reductase (MTHFR) C677T mutation. Arterioscler Thromb Vasc Biol 1996; 16: 878-82.
    CrossrefPubMedSearch in Google Scholar
  • 11 van Bockxmeer FM, Mamotte CDS, Vasikaran SD, Taylor RR. Methylenetetrahydrofolate reductase gene and coronary artery disease. Circulation 1997; 95: 21-4.
    CrossrefPubMedSearch in Google Scholar
  • 12 Brugada R, Marian AJ. A common mutation in methylenetetrahydrofolate reductase gene is not a major risk of coronary artery disease or myocardial infarction. Atherosclerosis 1997; 128: 107-12.
    CrossrefPubMedSearch in Google Scholar
  • 13 Dotter CT, Judkins MP. Transluminal treatment of arteriosclerotic obstruction: description of a new technique and a preliminary report of its application. Circulation 1964; 30: 654-70.
    CrossrefPubMedSearch in Google Scholar
  • 14 De Groote P, Bauters C, Mc Fadden E, Lablanche JM, Leroy F, Bertrand ME. Local lesion-related factors and restenosis after coronary angioplasty. Circulation 1995; 91: 968-72.
    CrossrefPubMedSearch in Google Scholar
  • 15 Sambrook J, Fritsch EF, Maniatis P. Molecular cloning. A laboratory manual. Cold Spring Harbour Laboratory Press; NY: 1989
    Search in Google Scholar
  • 16 Tunstall-Pedoe H, Kuulasmaa K, Amouyel P, Arveiler D, Rajakangas AM, Pajak A. Myocardial infarction and coronary deaths in the World Health Organization MONICA Project. Circulation 1994; 90: 583-612.
    CrossrefPubMedSearch in Google Scholar
  • 17 Renaud S, De Lorgeril M. Wine, alcohol, platelets, and the French paradox for coronary artery disease. Lancet 1992; 339: 1523-6.
    CrossrefPubMedSearch in Google Scholar
  • 18 Missiaglia E, Tosetto A, Rodeghiero F. The VITA project: risk of venous thromboembolism and C677T mutation of the MTHFR gene (abstract). Thromb Haemost. 1997 (suppl.): 393.
    PubMedSearch in Google Scholar
  • 19 De Stefano V, Chiusolo P, Paciaroni K, Casarelli I, Serra FG, Bizzi B, Leone G. Prevalence of factor V 1691 C to A and methylentetrahydrofolate reductase 677C to T mutated genes in patients with venous thrombosis (abstract). Thromb Haemost. 1997 (suppl): 569.
    PubMedSearch in Google Scholar
  • 20 Grandone E, Margaglione M, Calaizzo D, Cappucci G, Paladini D, Martinelli P, Montanaro S, Pavone G, Di Minno G. Factor V Leiden, C>T MTHFR polymorphism and genetic susceptibility to preeclampsia. Thromb Haemost 1997; 77: 1052-4.
    Thieme ConnectPubMedSearch in Google Scholar
  • 21 Annuario Statistico Italiano. 1996 ISTAT.
    PubMedSearch in Google Scholar
  • 22 Jacques P, Bostom A, Williams R. Relation between folate status, a common mutation in methylenetetrahydrofolate reductase and plasma homo-cysteine concentrations. Circulation 1996; 93: 7-9.
    CrossrefPubMedSearch in Google Scholar
  • 23 Mc Andrew P, Brandt JT, Pearl DK, Prior TW. The incidence of the gene for thermolabile methylene tetrahydrofolate reductase in African Americans. Thromb Res 1996; 83: 195-8.
    CrossrefPubMedSearch in Google Scholar
  • 24 Van der Put NMJ, Eskes AC, Blom HJ. Is the common 677 C → T mutation in the 5-10 methylenetetrahydrofolate reductase gene a risk factor for neural tube defects? A meta-analysis. Q J Med 1997; 90: 111-5.
    CrossrefPubMedSearch in Google Scholar
  • 25 Whitehead AS, Gallagher P, Mills JL, Kirke PN, burke H, Molloy AM, Weir DG, Shields DC, Scott JM. A genetic defect in 5-10 methylenetetrahydrofolate reductase in neural tube defects. Q J Med 1995; 88: 763-6.
    PubMedSearch in Google Scholar