title: Polymorphisms in folate pathway genes are not associated with somatic nondisjunction in turner syndrome.
abstract: Folate metabolism dysfunction can lead to DNA hypomethylation and abnormal chromosomal segregation. Previous investigations of this association have produced controversial results. Here we performed a case-control study in patients with Turner syndrome (TS) to determine the effects of genetic polymorphisms of folate pathway genes as potential risk factors for somatic chromosomal nondisjunction. TS is a useful model for this investigation because patients with TS show a high frequency of chromosome mosaicism. Here we investigated the possible association of polymorphisms of the MTHFR gene with TS risk, which has been previously investigated with controversial results. We also examined the effects of MTR, RFC1, and TYMS gene polymorphisms in TS for the first time. The risk was evaluated according to allelic and genotype (independent and combined) frequencies among 70 patients with TS and 144 age-matched healthy control subjects. Polymorphism genotyping was performed by PCR, PCR-RFLP, and PCR-ASA. The polymorphisms MTHFR 677C>T and 1298A>C, MTR 2756A>G, RFC1 80G>A, and TYMS 2R/3R-alone or in combinations-were not associated with the risk of chromosomal aneuploidy in TS. In conclusion, our present findings did not support a link between impaired folate metabolism and abnormal chromosome segregation leading to somatic nondisjunction in TS patients.
authors: Departamento de Genética, Universidade Federal de Pernambuco. Av. da Engenharia, S/N, Cidade Universitária, Recife, PE, Brazil.
authors: Adriana Valéria Sales
authors: AV
authors: Bispo
authors: Departamento de Genética, Universidade Federal de Pernambuco. Av. da Engenharia, S/N, Cidade Universitária, Recife, PE, Brazil.
authors: Luana Oliveira
authors: LO
authors: dos Santos
authors: Departamento de Genética, Universidade Federal de Pernambuco. Av. da Engenharia, S/N, Cidade Universitária, Recife, PE, Brazil.
authors: Juliana Vieira
authors: JV
authors: de Barros
authors: Unidade de Genética Pediátrica, Instituto de Medicina Integral Prof. Fernando Figueira (IMIP)-Recife, PE, Brasil.
authors: Andrea Rezende
authors: AR
authors: Duarte
authors: Unidade de Endocrinologia Pediátrica, Hospital das Cl, í, nicas HC/UFPE-Recife, PE, Brasil.
authors: Jacqueline
authors: J
authors: Araújo
authors: Centro de Oncohematologia Pediátrica de Pernambuco, Hospital Oswaldo Cruz/UPE-Recife, PE, Brasil.|Instituto de Ci, ê, ncias Biol, ó, gicas, UPE-Recife, PE, Brasil.
authors: Maria Tereza Cartaxo
authors: MT
authors: Muniz
authors: Departamento de Genética, Universidade Federal de Pernambuco. Av. da Engenharia, S/N, Cidade Universitária, Recife, PE, Brazil.
authors: Neide
authors: N
authors: Santos
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics; D003430:Cross-Sectional Studies; D020732:Cytogenetic Analysis; D005492:Folic Acid / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009630:Nondisjunction, Genetic / Q000235:genetics / Q000502:physiology*; D016017:Odds Ratio; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D051818:Replication Protein C / Q000235:genetics; D012307:Risk Factors; D015398:Signal Transduction / Q000235:genetics*; D013940:Thymidylate Synthase / Q000235:genetics; D014424:Turner Syndrome / Q000235:genetics*
chemical_list: C081632:RFC1 protein, human; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; C585801:MTR protein, human; C000600377:TYMS protein, human; D013940:Thymidylate Synthase; D051818:Replication Protein C
keywords: Aneuploidy; DNA hypomethylation; MTHFR; TYMS