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Human Reproduction, Vol. 17, No. 12, 3033-3036, December 2002
© 2002 European Society of Human Reproduction and Embryology

The transcobalamin codon 259 polymorphism influences the risk of human spontaneous abortion

H. Zetterberg1,5, B. Regland2, M. Palmér1, L. Rymo1, A. Zafiropoulos3, D.A. Arvanitis3, D.A. Spandidos3 and K. Blennow1,4

1 Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg University, S-413 45 Gothenburg, 2 Institute of Clinical Neuroscience, Psychiatry Section, Sahlgrenska University Hospital, Göteborg University, S-431 80 Mölndal, Sweden, 3 Department of Virology, Medical School, University of Crete, Heraklion, Crete, P.O. Box 1393, Greece and 4 Institute of Clinical Neuroscience, Department of Experimental Neuroscience, Sahlgrenska University Hospital, Göteborg University, S-431 80 Mölndal, Sweden

BACKGROUND: The remethylation cycle of methionine is folate and vitamin B12 (cobalamin) dependent and appears to be crucial for embryonic development, probably through effects on synthesis of DNA, proteins and polyamines. Transcobalamin (TC) transports vitamin B12 to the tissues. The objective of the present investigation was to explore the putative association between the major TC genetic polymorphism (Pro259Arg) and human spontaneous abortion. METHODS: The prevalence of the TC Pro259Arg polymorphism was determined in DNA samples from embryos that had been spontaneously aborted between the 6th and 20th week after conception, and adult controls using solid-phase minisequencing technique. RESULTS: The 259-Pro allele was significantly less frequent in the spontaneous abortion group than in the control group (42.2 and 57.0% respectively; P = 0.005), while the frequency of 259-Arg was significantly increased. There was a lower prevalence of 259-Pro homozygotes in the spontaneous abortion group compared with the control group (9.1 and 32.2% respectively; P < 0.001). CONCLUSIONS: The 259-Pro allele seems to have beneficial influences during embryogenesis, conceivably through its positive effect on vitamin B12 intracellular bioavailability. Our results warrant additional investigations addressing the question if vitamin B12 supplementation in addition to folic acid supplementation may prevent spontaneous abortion in women planning a pregnancy.

Key words: B12/homocysteine/polymorphism/spontaneous abortion/transcobalamin

5 To whom correspondence should be addressed. E-mail: henrik.zetterberg{at}clinchem.gu.se


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