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Molecular Biology Reports

, Volume 40, Issue 8, pp 4685–4689 | Cite as

Betaine–homocysteine methyltransferase 742G>A polymorphism and risk of down syndrome offspring in a Brazilian population

  • Márcia R. Amorim
  • Cláudia M. Moura
  • Aline D. Gomes
  • Hazel N. Barboza
  • Roberta B. Lopes
  • Márcia G. Ribeiro
  • Marcelo A. Costa LimaEmail author
Article

Abstract

Down syndrome (DS) is the most common form of mental retardation of genetic etiology. Several polymorphisms in genes involved with the folic acid cycle have been associated to the risk of bearing a DS child; however, the results are controversial. Betaine-homocysteine methyltransferase (BHMT) is a key enzyme of folate pathway, and catalyzes the remethylation of homocysteine into methionine. Recent studies suggest that the polymorphism BHMT 742G>A may be associated with a decreased risk of having a DS child. We herein investigate the association of this polymorphism with the occurrence of DS in a Brazilian population. We have genotyped 94 mothers of DS infants (DSM) and 134 control mothers (CM) for this polymorphism through PCR–RFLP, and found significant differences for both BHMT 742G>A genotype (P = 0.04) and allele (P = 0.03) frequencies between DSM and CM. The observed genotypic frequencies were GG = 0.45; GA = 0.45 and AA = 0.10 in CM, and GG = 0.54; GA = 0.38 and AA = 0.02 in DSM. Allelic frequencies were G = 0.68 and A = 0.32 in CM and G = 0.78 and A = 0.22 in DSM. The presence of the mutant BHMT 742 A allele decreases 40 % the risk of bearing a DS child (OR = 0.61; 95 % CI: 0.40–0.93; P = 0.03), and the risk is diminished up to >80 % in association with the homozygous genotype (OR = 0.17; 95 % CI: 0.04–0.80; P = 0.01). Our results indicate that women harboring the single nucleotide polymorphism BHMT 742G>A have a decreased risk of a DS pregnancy, and further studies are necessary to confirm this protective effect.

Keywords

Down syndrome BHMT 742G>A Folic acid metabolism Homocysteine remethylation 

Notes

Acknowledgments

We are grateful to the families that participate in this study and the IPPMG Pediatrics Clinic professionals. This study was supported by Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ E-26/110.427/2011).

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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Márcia R. Amorim
    • 1
  • Cláudia M. Moura
    • 2
  • Aline D. Gomes
    • 2
  • Hazel N. Barboza
    • 1
  • Roberta B. Lopes
    • 1
  • Márcia G. Ribeiro
    • 3
  • Marcelo A. Costa Lima
    • 2
    Email author
  1. 1.Departamento de Biologia GeralInstituto de Biologia, Universidade Federal FluminenseNiteróiBrazil
  2. 2.Laboratório de Genética Molecular Humana, Departamento de GenéticaInstituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro (UERJ)Rio de JaneiroBrazil
  3. 3.Instituto de Puericultura e Pediatria Martagão Gesteira, Universidade Federal do Rio de Janeiro, Cidade UniversitáriaRio de JaneiroBrazil

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