Skip to main content Accessibility help
×
Home

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

  • A. Chango (a1), G. Potier de Courcy (a2), F. Boisson (a1), J. C. Guilland (a3), F. Barbé (a1), M. O. Perrin (a1), J. P. Christidès (a2), K. Rabhi (a2), M. Pfister (a1), P. Galan (a2), S. Hercberg (a2) and J. P. Nicolas (a1)...

Abstract

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.

    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      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
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      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
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      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
      Available formats
      ×

Copyright

Corresponding author

Corresponding author: Dr J.P. Nicolas, fax +33 3 83 59 27 08 email jean-pierre.nicolas@medecine.uhp-nancy.fr

References

Hide All
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, 10491057.
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, 633641.
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, 11041110.
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, 99104.
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.
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, 593596.
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, 569573.
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, 722.
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, 102107.
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, 356361.
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, 9991001.
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, 111113.
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, 571577.
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, 336351.
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, 1728.
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, 79.
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, 10331039.
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, 15911593.
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, 186188.
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, 136143.
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, 263270.
Parodi, PW (1997) The French paradox unmasked: the role of folate. Medical Hypotheses 49, 313318.
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, 917920.
Rosenblatt, DS, (1995) Inherited disorders of folate transport and metabolism. In The Metabolic and Molecular Bases of Inherited Disease, pp. 31113128 [Scriver, CR, Beaudet, AL, Sly, WS and Valle, D, editors].New York: McGraw Hill.
Schneider, JA, Rees, DC, Liu, YT & Clegg, JB (1998) Worldwide distribution of a common methylenetetrahydrofolate reductase mutation. American Journal of Human Genetics 62, 12581260.
Selhub, J (1997) Mild hyperhomocysteinemia and arterial occlusive disease. Haematologica 82, 129132.
Ubbink, JB, Serfontein, WJ & de Villiers, LS (1986) Analytical recovery of protein-bound pyridoxal-5′-phosphate in plasma analysis. Journal of Chromatography 375, 399404.
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, 19271933.
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, 10441051.
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, 169172.
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, 14131418.

Keywords

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

  • A. Chango (a1), G. Potier de Courcy (a2), F. Boisson (a1), J. C. Guilland (a3), F. Barbé (a1), M. O. Perrin (a1), J. P. Christidès (a2), K. Rabhi (a2), M. Pfister (a1), P. Galan (a2), S. Hercberg (a2) and J. P. Nicolas (a1)...

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed