Hostname: page-component-586b7cd67f-dlnhk Total loading time: 0 Render date: 2024-11-23T03:00:26.244Z Has data issue: false hasContentIssue false
  • English
  • Français

5,10-methylenetetrahydrofolate reductase common mutations, folate status and plasma homocysteine in healthy French adults of the Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) cohort

Published online by Cambridge University Press:  09 March 2007

A. Chango ,
G. Potier de Courcy ,
F. Boisson ,
J. C. Guilland ,
F. Barbé ,
M. O. Perrin ,
J. P. Christidès ,
K. Rabhi ,
M. Pfister  and
P. Galan
...Show all authors
A. Chango
Affiliation:
Laboratoire de Biochimie Médicale et Pédiatrique, INSERM U-308, Faculté de Médecine, BP 184, F-54505 Vandœuvre-lès-Nancy, France
G. Potier de Courcy
Affiliation:
Institut Scientifique et Technique de la Nutrition et l'Alimentation, Conservatoire National des Arts et Métiers, Paris, France
F. Boisson
Affiliation:
Laboratoire de Biochimie Médicale et Pédiatrique, INSERM U-308, Faculté de Médecine, BP 184, F-54505 Vandœuvre-lès-Nancy, France
J. C. Guilland
Affiliation:
Laboratoire de Physiologie, Faculté de Médecine, Dijon, France
F. Barbé
Affiliation:
Laboratoire de Biochimie Médicale et Pédiatrique, INSERM U-308, Faculté de Médecine, BP 184, F-54505 Vandœuvre-lès-Nancy, France
M. O. Perrin
Affiliation:
Laboratoire de Biochimie Médicale et Pédiatrique, INSERM U-308, Faculté de Médecine, BP 184, F-54505 Vandœuvre-lès-Nancy, France
J. P. Christidès
Affiliation:
Institut Scientifique et Technique de la Nutrition et l'Alimentation, Conservatoire National des Arts et Métiers, Paris, France
K. Rabhi
Affiliation:
Institut Scientifique et Technique de la Nutrition et l'Alimentation, Conservatoire National des Arts et Métiers, Paris, France
M. Pfister
Affiliation:
Laboratoire de Biochimie Médicale et Pédiatrique, INSERM U-308, Faculté de Médecine, BP 184, F-54505 Vandœuvre-lès-Nancy, France
P. Galan
Affiliation:
Institut Scientifique et Technique de la Nutrition et l'Alimentation, Conservatoire National des Arts et Métiers, Paris, France
S. Hercberg
Affiliation:
Institut Scientifique et Technique de la Nutrition et l'Alimentation, Conservatoire National des Arts et Métiers, Paris, France
J. P. Nicolas*
Affiliation:
Laboratoire de Biochimie Médicale et Pédiatrique, INSERM U-308, Faculté de Médecine, BP 184, F-54505 Vandœuvre-lès-Nancy, France
*
†Corresponding author: Dr J.P. Nicolas, fax +33 3 83 59 27 08 email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The 677cytosine (c)→thymine(T) mutation identified in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene has been frequently associated with an elevated plasma homocysteine concentration. The aim of the present study was to determine the impact of this MTHFR common mutation on plasma and erythrocyte folate (RCF) and plasma total homocysteine (tHcy) concentrations in healthy French adults. A cohort of 291 subjects living in the Paris area and participating in the Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) study were analysed to assess the impact of MTHFR polymorphism 677C→T on folate status and plasma tHcy concentration. The frequency of the mutant homozygote for 677C→T polymorphism (677TT genotype) in the present cohort was 16·8%. There were significant differences in plasma tHcy between 677CC, 677CT and 677TT genotype groups. The RCF concentrations were significantly different between each genotype, the lowest levels being associated with the 677TT genotype. When segregated by gender, no differences in tHcy between homozygous 677TT, heterozygous 677CT and wild-type 677CC genotype groups in women were observed. The fasting tHcy in women was unrelated to the 677C→T mutation. However, tHcy was significantly increased in men with the homozygous 677TT genotype. We also analysed the possible implication of a second new MTHFR polymorphism (1298A→C) in subjects with mild hyperhomocysteinaemia (4th quartile of homocysteinaemia; tHcy >11·1 μmol/l). The polymorphism 1298A→C did not have a notable effect on tHcy or on the RCF levels. Our observations confirm a relatively high frequency of the 677TT genotype in the French population. Women with this genotype did not show the same increase in tHcy observed in men. In the present study dietary folate intake was not measured. Thus, the interaction of dietary folate with the MTHFR genotype in the French population needs further study.

Keywords

FolateHomocysteineMethylenetetrahydrofolate reductasePolymorphism
Type
Research Article
Information
British Journal of Nutrition , Volume 84 , Issue 6 , December 2000 , pp. 891 - 896
Copyright
Copyright © The Nutrition Society 2000

References

Boushey, J, Beresford, SAA, Omenn, GS & Motulsky, AG (1995) A quantitative assessment of plasma homocysteine as a risk factor for cardiovascular disease. Probable benefits of increasing folic acid intakes. Journal of the American Medical Association 274, 1049–1057.CrossRefGoogle ScholarPubMed
Brattström, L, Lindgren, A, Israelsson, B, Andersson, A & Hultberg, B (1994) Homocysteine and cysteine: determinants of plasma levels in middle-aged and elderly subjects. Journal of Internal Medicine 236, 633–641.CrossRefGoogle ScholarPubMed
Brönstrup, A, Hages, M, Prinz Langenohl, R & Pietrzik, K (1998) Effects of folic acid and combinations of folic acid and vitamin B-12 on plasma homocysteine concentrations in healthy, young women. American Journal of Clinical Nutrition 68, 1104–1110.CrossRefGoogle ScholarPubMed
Brouwer, IA, van Dusseldorp, M, Thomas, CMG, Duran, M, Hautvast, GAJ, Eskes, TKAB & Steegers-Theunissen, PM (1999) Low-dose folic acid supplementation decreases plasma homocysteine concentrations: a randomized trial. American Journal of Clinical Nutrition 69, 99–104.CrossRefGoogle ScholarPubMed
Chadefaux-Vakemans, B, Kara, MA & Thuillier, L (1996) Does the prevalent mutation 677C → T in the methylenetetrahydrofolate reductase gene account for hyperhomocysteine related to cardio-vascular disease?. Journal of Inherited Metabolism Disease 19, Suppl. 1, 25Abst.Google Scholar
Chango, A, Boisson, F, Barbé, F, Quilliot, D, Droesch, S, Pfister, M, Frémont, S, Rosenblatt, DS & Nicolas, JP (2000) The effect of 677C → T and 1298A → C mutations on plasma homocysteine and 5,10-methylenetetrahydrofolate reductase activity in healthy subjects. British Journal of Nutrition 83, 593–596.CrossRefGoogle ScholarPubMed
Christensen, B, Frosst, P, Lussier-Cacan, S, Selhub, J, Goyette, P, Rosenblatt, D, Genest, J Jr & Rozen, R (1997) Correlation of a common mutation in the methylenetetrahydrofolate reductase (MTHFR) gene with plasma homocysteine in patients with premature coronary artery disease. Arteriosclerosis Thrombosis and Vascular Biology 17, 569–573.CrossRefGoogle ScholarPubMed
Christidès, JP & Potier de Courcy, G (1987) Teneur en acide folique des aliments. 2–Optimisation du dosage microbiologique des folates dans les aliments (Folic acid content in food. 2–Optimization of microbiological assays for the determination of folate in food). Sciences des Aliments 7, 7–22.Google Scholar
Clarke, R, Woodhouse, P, Ulvik, A, Frost, C, Sherliker, P, Refsum, H, Ueland, PM & Khaw, KT (1998) Variability and determinants of total homocysteine concentrations in plasma in an elderly population. Clinical Chemistry 44, 102–107.CrossRefGoogle Scholar
den Heijer, M, Brouwer, IA & Bos, GMJ (1998) Vitamin supplementation reduces blood homocysteine levels. A controlled trial in patients with venous thrombosis and healthy volunteers. Arteriosclerosis Thrombosis and Vascular Biology 18, 356–361.CrossRefGoogle Scholar
Faure-Delanef, L, Quéré, I, Chassé, JF, Guerassimenko, O, Lesaulnier, M, Bellet, H, Zittoun, J, Kamoun, P & Cohen, D (1997) Methylenetetrahydrofolate reductase thermolabile variant and human longevity. American Journal of Human Genetics 60, 999–1001.Google ScholarPubMed
Frosst, P, Blom, HJ, Milos, R, Goyette, P, Sheppard, CA, Matthews, RG, Boers, GJA, den Heijer, M, Kluijtmans, LAJ, van den Heuvel, LP and Rozen, R (1995) A candidate genetic risk factor for vascular disease: a common mutation MTHFR. Nature Genetics 10, 111–113.CrossRefGoogle Scholar
Harmon, DL, Woodside, JV, Yarnell, JWG, McMaster, D, Young, IS, McCrum, EE, Gey, KF, Whitehead, AS & Evans, AE (1996) The common 'thermolabile' variant of methylenetetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia. Quarterly Journal of Medicine 89, 571–577.CrossRefGoogle Scholar
Hercberg, S, Préziosi, P, Briançon, S, Galan, P, Triol, I, Malvy, D, Roussel, A-M & Favier, A (1998) A primary prevention trial using nutritional doses of antioxidant vitamins and minerals in cardiovascular diseases and cancers in a general population: the SU.VI.MAX study-design, methods, and participant characteristics. Controlled Clinical Trials 19, 336–351.CrossRefGoogle Scholar
Hoffbrand, AV, Newcombe, FA & Mollin, DL (1966) Method of assay of red cell folate activity and the value of the assay as a test for folate deficiency. Journal of Clinical Pathology 19, 17–28.CrossRefGoogle ScholarPubMed
Jacques, PF, Bostom, AG, Williams, RR, Ellison, RC, Eckfeldt, JH, Rosenberg, IH, Selhub, J & Rozen, R (1996) Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 93, 7–9.CrossRefGoogle ScholarPubMed
Miller, JW, Nadeau, MR, Smith, D & Selhub, J (1994) Vitamin B6 deficiency vs folate deficiency: comparison of responses to methionine loading in rats. American Journal of Clinical Nutrition 55, 1033–1039.CrossRefGoogle Scholar
Molloy, AM, Daly, S, Mills, JL, Kirke, PN, Whitehead, AS, Ramsbottom, D, Conley, MR, Weir, DG & Scott, JM (1997) Thermolabile variant of 5,10-methylenetetrahydrofolate reductase associated with low red-cell folates: implications for folate intake recommendations. Lancet 349, 1591–1593.CrossRefGoogle ScholarPubMed
Molloy, AM, Mills, JL, Kirke, PN, Whitehead, AS, Weir, DG & Scott, JM (1998) Whole-blood folate values in subjects with different methylenetetrahydrofolate reductase genotypes: differences between the radioassay and microbiological assays. Clinical Chemistry 44, 186–188.CrossRefGoogle ScholarPubMed
Nygard, O, Refsum, H, Ueland, PM, Stensvold, I, Nordrehaug, JE, Kvale, G & Vollset, SE (1997) Coffee consumption and plasma total homocysteine: The Hordaland Homocysteine Study. American Journal of Clinical Nutrition 65, 136–143.CrossRefGoogle ScholarPubMed
Nygard, O, Refsum, H, Ueland, PM & Vollset, SE (1998) Major lifestyle determinants of plasma total homocysteine distribution: the Hordaland homocysteine study. American Journal of Clinical Nutrition 67, 263–270.CrossRefGoogle ScholarPubMed
Parodi, PW (1997) The French paradox unmasked: the role of folate. Medical Hypotheses 49, 313–318.CrossRefGoogle ScholarPubMed
Pepe, G, Comacho Vanegas, O, Giusti, B, Brunelli, T, Marcucci, R, Attanasio, M, Rickards, O, de Stefano, GF, Prisco, D, Gensini, GF & Abbate, R (1998) Heterogeneity in world distribution of the thermolabile C677T mutation in 5,10-methylenetetrahydrofolate reductase. American Journal of Human Genetics 63, 917–920.CrossRefGoogle ScholarPubMed
Rosenblatt, DS, (1995) Inherited disorders of folate transport and metabolism. In The Metabolic and Molecular Bases of Inherited Disease, pp. 3111–3128 [Scriver, CR, Beaudet, AL, Sly, WS and Valle, D, editors].New York: McGraw Hill.Google Scholar
Schneider, JA, Rees, DC, Liu, YT & Clegg, JB (1998) Worldwide distribution of a common methylenetetrahydrofolate reductase mutation. American Journal of Human Genetics 62, 1258–1260.CrossRefGoogle ScholarPubMed
Selhub, J (1997) Mild hyperhomocysteinemia and arterial occlusive disease. Haematologica 82, 129–132.Google ScholarPubMed
Ubbink, JB, Serfontein, WJ & de Villiers, LS (1986) Analytical recovery of protein-bound pyridoxal-5′-phosphate in plasma analysis. Journal of Chromatography 375, 399–404.CrossRefGoogle ScholarPubMed
Ubbink, JB, Vermaak, WJH, van der Merwe, A, Becker, PJ, Delport, R & Potgieter, HC (1994) Vitamin requirements for the treatment of hyperhomocysteinemia in humans. Journal of Nutrition 124, 1927–1933.CrossRefGoogle ScholarPubMed
van der Put, NMJ, Gabreëls, F, Stevens, MB, Smeitink, JAM, Trijbels, FJM, Eskes, TKAB, van der Heuvel, LP & Blom, HJ (1998) A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?. American Journal of Human Genetics 62, 1044–1051.CrossRefGoogle ScholarPubMed
Weisberg, I, Tran, P, Christensen, B, Sibani, S & Rozen, R (1998) A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Molecular Genetics and Metabolism 64, 169–172.CrossRefGoogle ScholarPubMed
Zittoun, J, Tonetti, C, Bories, D, Pignon, JM & Tullier, M (1998) Plasma homocysteine levels related to interactions between folate status and methylenetetrahydrofolate reductase: a study in 52 healthy subjects. Metabolism 47, 1413–1418.CrossRefGoogle ScholarPubMed