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Human Reproduction, Vol. 18, No. 11, 2460-2464, November 2003
© 2003 European Society of Human Reproduction and Embryology

Dizygotic twinning is not associated with methylenetetrahydrofolate reductase haplotypes

Grant W. Montgomery1,3, Zhen Zhen Zhao1, Katherine I. Morley1, Anna J. Marsh1, Dorret I. Boomsma2, Nicholas G. Martin1 and David L. Duffy1

1 Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia and 2 Psychology Department, Free University, Amsterdam, Netherlands

3 To whom correspondence should be addressed at: Queensland Institute of Medical Research, 300 Herston Rd, Herston, QLD 4006, Australia. e-mail grantM{at}qimr.edu.au

BACKGROUND: Folate metabolism is critical to embryonic development, influencing neural tube defects (NTD) and recurrent early pregnancy loss. Polymorphisms in 5,10-methylenetetrahydrofolate reductase (MTHFR) have been associated with dizygotic (DZ) twinning through pregnancy loss. METHODS: The C677T and A1298C polymorphisms in MTHFR were genotyped in 258 Australasian families (1016 individuals) and 118 Dutch families (462 individuals) of mothers of DZ twins and a population sample of 462 adolescent twin families (1861 individuals). Haplotypes were constructed from the alleles, and transmission of the MTHFR haplotypes to mothers of DZ twins and from parents to twins in the adolescent twin families analysed. RESULTS: The C677T and A1298C were common in all three populations (frequencies > 0.29). There was strong linkage disequilibrium (D' = 1) between the variants, showing that specific combinations of alleles (haplotypes) were transmitted together. Three haplotypes accounted for nearly all the variation. There was no evidence of any association between MTHFR genotype and twinning in mothers of twins, or of the loss of specific MTHFR genotypes during twin pregnancies. CONCLUSIONS: It is concluded that variation in twinning frequency is not associated with MTHFR genotype.

Key words: DZ twins/MTHFR/polymorphisms/twinning frequency


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