Fertility and Sterility
Volume 91, Issue 1 , Pages 56-61 , January 2009

Common 677C→T mutation of the 5,10-methylenetetrahydrofolate reductase gene affects follicular estradiol synthesis

  • Stephanie Hecht

      Affiliations

    • Department of Obstetrics and Gynecology, Division of Endocrinology and Reproductive Medicine, Grosshadern, Ludwig Maximilians-University, Munich, Germany
    • ,
  • Roman Pavlik

      Affiliations

    • Department of Obstetrics and Gynecology, Division of Endocrinology and Reproductive Medicine, Grosshadern, Ludwig Maximilians-University, Munich, Germany
    • ,
  • Peter Lohse, M.D.

      Affiliations

    • Department of Clinical Chemistry, Grosshadern, Ludwig Maximilians-University, Munich, Germany
    • ,
  • Ulrich Noss, M.D.

      Affiliations

    • Centre for Reproductive Medicine, Munich, Germany
    • ,
  • Klaus Friese, M.D.

      Affiliations

    • Department of Obstetrics and Gynecology, Division of Endocrinology and Reproductive Medicine, Grosshadern, Ludwig Maximilians-University, Munich, Germany
    • ,
  • Christian J. Thaler, M.D.

      Affiliations

    • Department of Obstetrics and Gynecology, Division of Endocrinology and Reproductive Medicine, Grosshadern, Ludwig Maximilians-University, Munich, Germany
    • Corresponding Author InformationReprint requests: Christian J. Thaler, M.D., Department of Obstetrics and Gynecology, Division of Endocrinology and Reproductive Medicine, Grosshadern, Ludwig-Maximilians-University, Marchioninistrasse 15, D-81377 Munich, Germany (FAX: 49-89-7095-7588).

Received 14 March 2007 ,Revised 5 November 2007 ,Accepted 5 November 2007.

References 

  1. Ueland PM, Hustad S, Schneede J, Refsum H, Vollset SE. Biological and clinical implications of the MTHFR C677T polymorphism. Trends Pharmacol Sci. 2001;22:195–201
  2. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10:111–113
  3. Finnell RH, Greer KA, Barber RC, Piedrahita JA. Neural tube and craniofacial defects with special emphasis on folate pathway genes. Crit Rev Oral Biol Med. 1998;9:38–53
  4. van der Put NM, Steegers-Theunissen RP, Frosst P, Trijbels FJ, Eskes TK, van den Heuvel LP, et al. Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida. Lancet. 1995;346:1070–1071
  5. James SJ, Pogribna M, Pogribny IP, Melnyk S, Hine RJ, Gibson JB, et al. Abnormal folate metabolism and mutation in the methylenetetrahydrofolate reductase gene may be maternal risk factors for Down syndrome. Am J Clin Nutr. 1999;70:495–501
  6. Ray JG, Laskin CA. Folic acid and homocyst(e)ine metabolic defects and the risk of placental abruption, pre-eclampsia and spontaneous pregnancy loss: a systematic review. Placenta. 1999;20:519–529
  7. Hasbargen U, Lohse P, Thaler CJ. The number of dichorionic twin pregnancies is reduced by the common MTHFR 677C→T mutation. Hum Reprod. 2000;15:2659–2662
  8. Thaler CJ, Budiman H, Ruebsamen H, Nagel D, Lohse P. Effects of the common 677C→T mutation of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene on ovarian responsiveness to recombinant follicle-stimulating hormone. Am J Reprod Immunol. 2006;55:251–258
  9. Best CL, Pudney J, Anderson DJ, Hill JA. Modulation of human granulosa cell steroid production in vitro by tumor necrosis factor alpha: implications of white blood cells in culture. Obstet Gynecol. 1994;84:121–127
  10. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248–254
  11. Kossoy LR, Hill GA, Gettys TW, Brodie BL, Herbert CM, Wentz AC. Results of in-vitro fertilization in normal ovulatory women treated with pure follicle stimulating hormone. Analysis of the oestradiol response. Hum Reprod. 1989;4:754–756
  12. Sharp L, Little J. Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review. Am J Epidemiol. 2004;159:423–443
  13. Laird PW. The power and the promise of DNA methylation markers. Nat Rev Cancer. 2003;3:253–266
  14. Eden A, Gaudet F, Waghmare A, Jaenisch R. Chromosomal instability and tumors promoted by DNA hypomethylation. Science. 2003;300:455
  15. van GC, Stehouwer CD. Homocysteine-lowering treatment: an overview. Expert Opin Pharmacother. 2001;2:1449–1460
  16. Malinow MR, Nieto FJ, Kruger WD, Duell PB, Hess DL, Gluckman RA, et al. The effects of folic acid supplementation on plasma total homocysteine are modulated by multivitamin use and methylenetetrahydrofolate reductase genotypes. Arterioscler Thromb Vasc Biol. 1997;17:1157–1162

 Authors S.H. and R.P. contributed equally to the work and both should be considered to be the first author.

 Supported by the Department of Obstetrics and Gynecology, Grosshadern, Ludwig-Maximilians-University, Munich, Germany.

 Presented at the 56th National Congress of Gynecology and Obstetrics, Berlin, Germany, September 19–22, 2006.

PII: S0015-0282(07)03976-3

doi: 10.1016/j.fertnstert.2007.11.011

Fertility and Sterility
Volume 91, Issue 1 , Pages 56-61 , January 2009

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