title: The MTR 2756A>G polymorphism and maternal risk of birth of a child with Down syndrome: a case-control study and a meta-analysis.
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.
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via S. Giuseppe 22, 56126, Pisa, IT, Italy, f.coppede@geog.unipi.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Coppedè
authors.forename: Paolo
authors.initials: P
authors.lastname: Bosco
authors.forename: Valentina
authors.initials: V
authors.lastname: Lorenzoni
authors.forename: Francesca
authors.initials: F
authors.lastname: Migheli
authors.forename: Concetta
authors.initials: C
authors.lastname: Barone
authors.forename: Ivana
authors.initials: I
authors.lastname: Antonucci
authors.forename: Liborio
authors.initials: L
authors.lastname: Stuppia
authors.forename: Corrado
authors.initials: C
authors.lastname: Romano
authors.forename: Lucia
authors.initials: L
authors.lastname: Migliore
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D016001:Confidence Intervals; D003710:Demography; D004314:Down Syndrome / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy; D053858:Metabolic Networks and Pathways / Q000235:genetics; D016017:Odds Ratio; D036801:Parturition / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
chemical_list: D005492:Folic Acid; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; C585801:MTR protein, human