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The MTRR 66A>G polymorphism and maternal risk of birth of a child with Down syndrome in Caucasian women: a case–control study and a meta-analysis

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Abstract

We performed a large case–control study and a meta-analysis of the literature to address the role of the methionine synthase reductase (MTRR) c.66A>G polymorphism as a maternal risk factor for the birth of a child with Down Syndrome (DS) among Caucasian women. A total of 253 mothers of a DS child (MDS) and 298 control mothers of Italian origin were included in the case–control study. The meta-analysis of previous and present data involved a total of seven studies performed in Caucasian populations (971 MDS and 1,387 control mothers). Results from the meta-analysis indicated overall a positive significant association between MTRR c.66A>G genotype [OR 1.36 (95 % CI 1.10–1.68), dominant model] and allele frequencies [OR 1.26 (95 % CI 1.04–1.51), allele contrast model] and maternal risk of birth of a child with DS. A sensitivity analysis revealed some interesting differences between Europeans, Caucasians of European descent, and inhabitants of Mediterranean regions, suggesting the possibility of population-specific modifying factors. The case–control study revealed association of the polymorphism with increased folate levels, and a possible interaction with the methionine synthase (MTR) c.2756A>G one, that resulted in a borderline significant maternal risk of birth of a child with DS for the double heterozygous MTR 2756AG/MTRR 66AG genotype [OR 1.79 (95 % CI 1.00–3.18)]. Overall, present data suggest that the MTRR c.66A>G polymorphism represents a risk factor for the birth of a child with DS among white Caucasian women. However, the combined presence of other genetic factors and interactions with geographic and environmental ones, can modify the effect of the single polymorphism alone, leading to population specific effect sizes.

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Acknowledgments

The study was supported by the Italian Ministry of Health (Ricerca Corrente 2012 entitled “Le malattie genetiche con ritardo mentale”) and “5 per mille” funding. We 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 Roma 55, 56126, Pisa, Italy

    Fabio Coppedè, Maria Denaro & 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, Guido Anello, 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

  5. Interdepartmental Research Center Nutrafood “Nutraceuticals and Food for Health”, University of Pisa, Pisa, Italy

    Fabio Coppedè & Lucia Migliore

Authors
  1. Fabio Coppedè
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  2. Paolo Bosco
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  10. Lucia Migliore
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Correspondence to Fabio Coppedè.

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Coppedè, F., Bosco, P., Lorenzoni, V. et al. The MTRR 66A>G polymorphism and maternal risk of birth of a child with Down syndrome in Caucasian women: a case–control study and a meta-analysis. Mol Biol Rep 41, 5571–5583 (2014). https://doi.org/10.1007/s11033-014-3462-5

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  • DOI: https://doi.org/10.1007/s11033-014-3462-5

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