RESUMO
BACKGROUND: The 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and low folate levels are associated with inhibition of DNA methyltransferase and consequently DNA hypomethylation. The expanding spectrum of common conditions linked with MTHFR polymorphisms includes certain adverse birth outcome, pregnancy complications, cancers, adult cardiovascular diseases and psychiatric disorders, with several of these associations remaining still controversial. Trisomy 21 or Down syndrome (DS) is the most common genetic cause of mental retardation. It stems predominantly from the failure of chromosome 21 to segregate normally during meiosis. Despite substantial research, the molecular mechanisms underlying non-disjunction leading to trisomy 21 are poorly understood. MATERIALS AND METHODS: Two common variants C677T and A1298C of the MTHFR gene were screened in 36 parents with DS children and 60 healthy couples from Tamil Nadu and Karnataka. The MTHFR genotypes were studied by RFLP analysis of PCR-amplified products and confirmed by sequencing. RESULTS: The CT genotype was seen in three each (8.3%) of case mothers and fathers. One case father showed TT genotype. All the control individuals exhibited the wild type CC genotype. A similar frequency for the uncommon allele C of the second polymorphism was recorded in case mothers (0.35) and fathers (0.37) in comparison with the control mothers (0.39) and fathers (0.37). CONCLUSION: This first report on MTHFR C677T and A1298C polymorphisms in trisomy 21 parents from south Indian population revealed that MTHFR 677CT polymorphism was associated with a risk for Down syndrome.
Assuntos
Adolescente , Alelos/análise , Criança , Síndrome de Down/genética , Pai , Feminino , Estudos de Associação Genética/métodos , Variação Genética/genética , Genótipo , Humanos , Índia/epidemiologia , Lactente , Deficiência Intelectual/genética , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Grupos Populacionais/genética , Grupos Populacionais/genéticaRESUMO
Methylenetetrahydrofolate reductase (MTHFR: EC 1.5.1.20) polymorphisms are associated to acute lymphoid leukemia in different populations. We used the polymerase chain reaction and the restriction fragment length polymorphism method (PCR-RFLP) to investigate MTHFR C677T and A1298C polymorphism frequencies in 67 patients with chronic myeloid leukemia (CML), 27 with acute myeloid leukemia FAB subtype M3 (AML-M3) and 100 apparently healthy controls. The MTHFR mutant allele frequencies were as follows: CML = 17.2 percent for C677T, 21.6 percent for A1298C; AML-M3 = 22.2 percent for C677T, 24.1 percent for A1298C; and controls = 20.5 percent for C677T, 21 percent for A1298C. Taken together, our results provide evidence that MTHFR polymorphisms have no influence on the development of CML or AML-M3.