American Journal of Obstetrics & Gynecology
Volume 182, Issue 5 , Pages 1258-1263 , May 2000

A common mutation in the 5,10-methylenetetrahydrofolate reductase gene as a new risk factor for placental vasculopathy

Received 31 December 1998 ,Revised 19 November 1999 ,Accepted 19 December 1999.

References 

  1. Mudd SH, Levy HL, Skovby F. Disorders of transsulfuration. In:  Scriver CR,  Beaudet AL,  Sly WS,  Valle D editor. The metabolic and molecular bases of inherited disease. New York: McGraw-Hill; 1995;p. 1279–1327
  2. Ueland PM, Refsum H, Brattström L. Plasma homocysteine and cardio-vascular disease. In:  Francis RB editors. Atherosclerotic cardiovascular disease, hemostasis, and endothelial function. New York: Marcel Dekker; 1992;p. 183–1136
  3. Den Heijer M, Koster T, Blom HJ, Bos GM, Briët E, Reitsma PH, et al.  Hyperhomocysteinemia as a risk factor for deep-vein thrombosis. N Engl J Med. 1996;334:759–762
  4. Mills JL, McPartlin JM, Kirke PN, Lee YJ, Conley MR, Weir DG, et al.  Homocysteine metabolism in pregnancies complicated by neural tube defects. Lancet. 1995;345:149–151
  5. Wouters MG, Boers GH, Blom HJ, Trijbels FJ, Thomas CM, Borm GF, et al.  Hyperhomocysteinemia: a risk factor in women with unexplained recurrent early pregnancy loss. Fertil Steril. 1993;60:120–125
  6. Goddijn-Wessel TA, Wouters MG, van de Molen EF, Spuijbroek MD, Steegers-Theunissen RP, Blom HJ, et al.  Hyperhomocysteinemia: a risk factor for placental abruption or infarction. Eur J Obstet Gynecol Reprod Biol. 1996;66:23–29
  7. Dekker GA, De Vries JI, Doelitzsch PM, Huijgens PC, Von Blomberg BM, Jakots C, et al.  Underlying disorders associated with severe early-onset preeclampsia. Am J Obstet Gynecol. 1995;173:1042–1048
  8. Kluijtmans LA, Van den Heuvel LP, Boers GH, Frosst P, Stevens EM, Van Oost A, 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
  9. 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
  10. Jacques PF, Bostom AG, Williams RR, Ellison RC, Eckfeldt JH, Rosenberg IH, et al.  Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation. 1996;93:7–9
  11. Van der Put NM, Steegers-Theunissen RP, Frosst P, Trijbels JM, Eskes TK, Van den Heuvel LP, et al.  Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida. Lancet. 1995;346:1070–1071
  12. 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
  13. Macpherson T. Fact and fancy: what can we really tell from the placenta?. Arch Pathol Lab Med. 1991;115:672–681
  14. Domisse J, Tiltman AJ. Placental bed biopsies in placental abruption. Br J Obstet Gynaecol. 1992;99:651–654
  15. Rayne SC, Kraus FT. Placental thrombi and other vascular lesions: classification, morphology, and clinical correlations. Pathol Res Pract. 1993;189:2–17
  16. Ananth CV, Savitz DA, Williams MA. Placental abruption and its association with hypertension and prolonged rupture of membranes: a methodological review and meta-analysis. Obstet Gynecol. 1996;88:309–318
  17. Naeye RL. Maternal age, obstetric complications, and the outcome of pregnancy. Obstet Gynecol. 1983;61:210–216
  18. te Poele-Pothoff MT, van den Berg M, Franken DG, Boers GH, Jakobs C, de Kroon IF, et al.  Three different methods for the determination of total homocysteine in plasma. Ann Clin Biochem. 1995;32(Pt 2):218–220
  19. Mooij PN, Thomas CM, Doesburg WH, Eskes TK. Multivitamin supplementation in oral contraceptive users. Contraception. 1991;44:277–288
  20. Steegers-Theunissen RP, Boers GH, Steegers EA, Trijbels FJ, Thomas CM, Eskes TK. Effects of sub-50 oral contraceptives on homocysteine metabolism: a preliminary study. Contraception. 1992;45:129–139
  21. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215
  22. Kluijtmans LA, Kastelein JJ, Lindemans J, Boers GH, Heil SG, Bruschke AV, et al.  Thermolabile methylenetetrahydrofolate reductase in coronary artery disease. Circulation. 1997;96:1573–1577
  23. Whitehead AS, Gallagher P, Mills JL, Kirke PN, Burke H, Molloy AM, et al.  A genetic defect in 5,10 methylenetetrahydrofolate reductase in neural tube defects. QJM. 1995;88:763–766
  24. Nelen WL, van der Molen EF, Heil SG, Blom HJ, Eskes TK, Steegers EA. Recurrent early pregnancy loss and genetic related disturbances in folate and homocysteine metabolism. Br J Hosp Med. 1997;58:511–513
  25. Sodha S, Arinami T, Hamada H, Yamada N, Hamaguchi H, Kubo T. Methylenetetrahydrofolate reductase polymorphism and pre-eclampsia. J Med Genet. 1997;34:525–526
  26. MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet. 1991;338:131–137

 Supported by grants 94.029 and D97.021 from the Dutch Heart Foundation, The Hague, the Netherlands.

☆☆ Reprint requests: Henk J. Blom, PhD, Department of Paediatrics, University Hospital Nijmegen PO Box 9101, 6500 HB Nijmegen, The Netherlands.

PII: S0002-9378(00)70194-3

doi: 10.1067/mob.2000.105199

American Journal of Obstetrics & Gynecology
Volume 182, Issue 5 , Pages 1258-1263 , May 2000