Associa????o de polimorfismos nos genes da metilenotetrahidrofolatoredutase, metionina sintase, cistationina beta-sintetase e micronutrientesrelacionados ?? via metab??lica da homociste??na em m??es e rec??m-nascidos do Estado da Bahia

N??veis elevados de homociste??na (Hcy) no plasma t??m sido associados ?? presen??a de polimorfismo no gene da Metilenotetrahidrofolato Redutase (MTHFR), Metionina Sintase (MS) e Cistationina beta Sintetase (CBS) ou relacionados com quadros nutricionais, que podem alterar uma das duas vias metab??licas que envolvem os precursores do metabolismo da Hcy, remetila????o ou trans-sulfura????o. Desta forma, os polimorfismos g??nicos associados ao metabolismo da vitamina B12, folato podem conferir n??veis elevados de homociste??na, assim como diminui????o nos n??veis de folato e vitamina B12 plasm??tico, produzindo complica????es durante a gravidez bem como, altera????es na metila????o do DNA e conseq??entemente evoluir para doen??as card??acas, vasculares, c??ncer, s??ndrome de Down, defeitos de fechamento de tubo neural e baixo peso ao nascer. Considerando o metabolismo anormal de folato, vitamina B12 e homociste??na ??s muta????es do gene de enzimas envolvidas no metabolismo destes podem ser marcadores de fatores de risco materno. O objetivo deste trabalho foi investigar em 240 m??es e 240 rec??m-nascidos (RNs) associa????es entre os polimorfismos presentes em genes respons??veis no metabolismo da homociste??na e seus substratos caracterizando de forma hematol??gica, bioqu??mica e molecular. Foram investigados os polimorfismos C677T e A1298C no gene da MTHFR; A2756G no gene da metionina sintase (MS) e a inser????o 844ins68 no gene da enzima cistationina beta sintetase (CBS), utilizando a t??cnica de PCR ??? RFLP. Os n??veis s??ricos de homociste??na, vitamina B12 e folatos foram determinados pela t??cnica de quimioluminesc??ncia. As freq????ncias al??licas dos polimorfismos entre 191 m??es e 226 rec??m-nascidos foram 27,7%. e 25,6%, respectivamente, para o polimorfismo C677T da MTHFR; 14,0% e 14,6%, respectivamente, para o polimorfismo A1298C da MTHFR; 23,9% e 24,5%, respectivamente, para o polimorfismo A2756G da MS; e 22,3% e 20,2%, respectivamente, para a inser????o 844ins68 da CBS. Os n??veis de Folatos e Vitamina B12 entre m??es normais e portadores para os diversos gen??tipos estudados n??o demonstraram diferen??as estatisticamente significativas. Por??m, para os RNs diferen??as estatisticamente significantes foram encontradas para os portadores do polimorfismo A2756G e n??veis de vitamina B12 (p=0,0023). Diferen??as estat??sticas significantes foram encontradas entre m??es normais e portadores para o polimorfismo A1298C e n??veis de homociste??na (p=0,0002). Tamb??m foram encontradas diferen??as estatisticamente significantes para a ocorr??ncia dos polimorfismos C667T da MTHFR e valores de leuc??citos (p=0,0482); A2756G da MS e valores de leuc??citos (p=0,0168) e de Ht (p=0,0103); e 844ins68 da CBS e valores de Hb (p=0,0432) no grupo de m??es.Para o grupo de RNs os dados hematol??gicos apresentaram signific??ncia estat??stica apenas entre os valores de plaquetas (p=0,0247) e HCM (p=0,0278) e o polimorfismo A1298C. Os resultados deste estudo contribuem para o entendimento de fatores gen??ticos relacionados com nutrientes indicando a grande import??ncia de apontar os fatores de risco que possam ser prevenidos e definir estrat??gias intervencionistas que reduzam os riscos maternos, bem como os cuidados que devem ser tomados durante o acompanhamento pedi??trico relacionado aos n??veis s??ricos de Vitamina B12 e folatos e a ocorr??ncia de altera????es gen??ticas de enzimas, uma vez que a presen??a destas pode conduzir a associa????o de riscos relacionados a doen??as gen??ticas.High levels of homocysteine (Hcy) in plasma have been associated with the presence of the polymorphism in the gene MTHFR, Methionine Synthase (MS) and Cystathionine beta Synthase (CBS) or related to nutrition tables, which can alter one of two metabolic pathways involving the precursors of metabolism of Hcy, remethylation or trans-sulphuration. Thus the gene polymorphisms associated with the metabolism of vitamin B12, folate can give high levels of homocysteine, as well as reduction in the levels of folate and vitamin B12 plasma, producing complications during pregnancy as well as changes in methylation of DNA and thus evolve into heart disease, vascular, cancer, Down syndrome, defects in the neural tube closure and low birth weight. Considering the abnormal metabolism of folate, vitamin B12 and homocysteine to mutations of the gene of enzymes involved in the metabolism of these can be markers of risk factors mother. The research aimed to investigate in 240 mothers and 240 newborns (NBs) associations between polymorphisms in these genes responsible for the metabolism of homocysteine and their way of characterizing substrates hematological, biochemical and molecular. We investigated the C677T and A1298C polymorphisms in the gene MTHFR; A2756G in the gene of methionine synthase (MS) and 844ins68 insertion in the gene of the enzyme cystathionine beta synthase (CBS), using the technique of PCR - RFLP. Serum levels of homocysteine, vitamin B12 and folate were determined by the technique of chemiluminescences. Allelic frequencies of polymorphisms between 191 mothers and 226 newborns were 27.7%. and 25.6% respectively, for the MTHFR C677T polymorphism, 14.0% and 14.6% respectively in the A1298C of MTHFR polymorphism, 23.9% and 24.5% respectively in the A2756G polymorphism of MS, and 22.3% and 20.2% respectively in the integration of CBS 844ins68. The levels of Folate and Vitamin B12 between mothers and normal carriers for the various genotypes studied showed no statistically significant differences. But for NBs statistically significant differences were found to carry the A2756G polymorphism and levels of vitamin B12 (p = 0.0023). Significant statistical differences were found between normal and mothers bearers for the polymorphism A1298C and levels of homocysteine (p=0.0002).Were also found statistically significant differences in the occurrence of the MTHFR C667T polymorphism and values of white blood cells (p = 0.0482); A2756G of MS and values of white blood cells (p = 0.0168) and Ht (p = 0.0103) and 844ins68 of CBS and values of Hb (p = 0.0432) in the group of mothers. For the group of NBs data hematological statistically significant only between the values of platelets (p = 0.0247) and HCM (p = 0.0278) and A1298C polymorphism. The results of this study contribute to the understanding of genetic factors related nutrients indicating the great importance of pointing the risk factors that can be prevented and interventionist strategies that reduce risks maternal, and the care that must be taken during the pediatric related to the serum levels of vitamin B12 and folate and the occurrence of genetic modification of enzymes, since the presence of these can lead to association of risks related to genetic diseases