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The MTR 2756A>G polymorphism and maternal risk of birth of a child with Down syndrome: a case–control study and a meta-analysis

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Abstract

Methionine synthase (MTR) is required for the conversion of homocysteine (hcy) to methionine in the one-carbon metabolic pathway. Previous studies investigating a common MTR 2756A>G polymorphism as a maternal risk factor for the birth of a child with Down syndrome (DS) are conflicting and limited by small case–control cohorts, and its contribution to circulating hcy levels is still debated. We performed a large case–control study and a meta-analysis of the literature to further address the role of MTR 2756A>G as a maternal risk factor for the birth of a child with DS. 286 mothers of a DS child (MDS) and 305 control mothers of Italian origin were included in the case–control study. Genotyping was performed by means of PCR/RFLP technique. Data on circulating levels of hcy, folates, and vitamin B12 were available for 189 MDS and 194 control mothers. The meta analysis of previous and present data involved a total of 8 studies (1,171 MDS and 1,402 control mothers). Both the case–control study and the meta-analysis showed no association of MTR 2756A>G with the maternal risk of birth of a child with DS (OR = 1.15; 95 % CI 0.85–1.55, and OR = 1.08; 95 % CI 0.93–1.25, respectively), even after stratification of the overall data available for the meta-analysis into ethnic groups. No association of the studied polymorphism with circulating levels of hcy, folates, and vitamin B12 was observed. Present data do not support a role for MTR 2756A>G as independent maternal risk factor for a DS birth.

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Acknowledgments

This work was partially supported by the following funds: Italian Ministry of Health (Ricerca Corrente 2012 entitled “Le malattie genetiche con ritardo mentale”) and “5 per mille” funding. The authors acknowledge Dr. S. Bargagna from IRCCS Stella Maris (Calambrone, PI) for her help in collecting MDS subjects from Pisa.

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Authors and Affiliations

  1. Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via S. Giuseppe 22, 56126, Pisa, IT, Italy

    Fabio Coppedè, Francesca Migheli & Lucia Migliore

  2. IRCCS, Oasi Maria SS Institute for Research on Mental Retardation and Brain Aging, Via Conte Ruggero 73, 94018, Troina, Italy

    Paolo Bosco, Concetta Barone & Corrado Romano

  3. Institute of Management, Sant’Anna School of Advanced Studies, 56126, Pisa, Italy

    Valentina Lorenzoni

  4. “DISPUTer” Department of Psychological, Humanistic and Territorial Sciences, “Gabriele d’Annunzio” University of Chieti, Chieti, Italy

    Ivana Antonucci & Liborio Stuppia

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  1. Fabio Coppedè
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  2. Paolo Bosco
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  3. Valentina Lorenzoni
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  4. Francesca Migheli
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  9. Lucia Migliore
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Correspondence to Fabio Coppedè.

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Coppedè, F., Bosco, P., Lorenzoni, V. et al. The MTR 2756A>G polymorphism and maternal risk of birth of a child with Down syndrome: a case–control study and a meta-analysis. Mol Biol Rep 40, 6913–6925 (2013). https://doi.org/10.1007/s11033-013-2810-1

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