Estudo dos polimorfismos 677C>T E 1298 A>C do gene da metileno tetrahidrofolato redutase e 66A>G do gene da metionina sintase redutase e a relação com a ocorrência da síndrome de Down / Study of polymorphisms 677C> TE 1298 A> C gene and methylenetetrahydrofolate reductase 66A> G gene and the methionine synthase reductase relation to the occurrence of Down syndrome

A Síndrome de Down (SD) é a mais freqüente anormalidade cromossômica em nativivos e é causada pela presença de um cromossomo 21 extra. A prevalência é de aproximadamente 1/600 nascidos vivos. Polimorfismos nos genes da Metilenetetrahidrofolato Redutase (MTHFR) e da Metionina Sintase Redutase (MTRR), enzimas centrais do metabolismo do folato que afetam a metilação e síntese do DNA, podem ser fatores de risco para a ocorrência da SD. Detectar as freqüências dos polimorfismos 677C >T e 1298A>C do gene da MTHFR e 66A>G do gene da MTRR e associar com a ocorrência de SD. Para o estudo de caso-controle, DNA genômico foi isolado a partir de sangue periférico de 61 mães de crianças com SD, 56 afetados, 28 pais e 102 mulheres controles. Para estudo de corte transversal, 300 amostras de DNA pertencentes de indivíduos da população geral de Salvador foram analisadas. Para análise dos polimorfismos, foram utilizadas as técnicas de PCR e RFLP. Resultados: No estudo de caso-controle, a freqüência do alelo T, da mutação 677C>T da MTHFR, foi de 0,24 entre as crianças com SD; 0,3 entre as mães e 0,25 entre os pais. A freqüência do alelo C, da mutação 1298A>C da MTHFR, foi de 0,2 entre as crianças com SD; 0,16 entre as mães e 0,16 entre os pais. A freqüência do alelo G, da mutação MTRR 66A>G foi de 0,33 entre as crianças com SD; 0,35 entre as mães e 0,46 entre os pais. Entre as mulheres controles, as freqüências dos alelos T, C e G dos genes da MTHFR 677C>T, MTHFR 1298A>C e MTRR66A>G foram de 0,25; 0,15 e 0,25, respectivamente. Comparando as freqüências alélicas das mães de crianças com SD e com as controles, não foi observada diferença estatisticamente significante, sugerindo que neste estudo os polimorfismos investigados não influenciam na ocorrência da SD, bem como a idade materna não sugere ser fator de risco aumentado para a SD, uma vez que a maioria dos filhos com SD eram provenientes de mães com idade materna inferior a 35 anos...

Down Syndrome (DS) is one of the most frequent chromosomal abnormalities inhumans and is caused by the presence of an extra chromosome 21. Its prevalence is approximately 1/600 live births. Genetic polymorphisms in MethylenetetrahydrofolateReductase (MTHFR) and Methionine Synthase Reductase (MTRR) the central enzymes in folate metabolism that affects DNA methylation and synthesis may be risk factors to cause DS. Objective: To detect MTHFR 677C>T, 1298A>C and MTRR 66A>G polymorphisms frequencies and associate with the DS occurrence. Methods: For casecontrol study, genomic DNA was isolated from the peripheral blood of 61 mothers of children with DS, 56 affected, 28 fathers and 102 control women. For cross-sectional study, 300 genomic DNA samples were analyzed. PCR and RFLP were used to examinethe polymorphisms. Results: The MTHFR 677C>T mutation showed T allelefrequencies of 0.24 among DS children; 0.3 among their mothers and 0.25 among their fathers. The MTHFR 1298A>C mutation showed C allele frequencies of 0.2 among DS children; 0.16 among their mothers and 0.16 among their fathers. The MTRR A>G mutation showed G allele frequencies of 0.33 among DS children; 0.35 among their mothers and 0.46 among their fathers. Among control women, T, C and G allele’s frequencies were 0.25, 0.15 and 0.25, respectively. When allele frequencies were compared between control and DS mothers no significant difference statistical was observed what suggests that the studied polymorphisms had no influence in DS as well as maternal age suggests not be risk factor to this disorder...

Re-mapping the molecular features of the human immunodeficiency virus type 1 and human T-cell lymphotropic virus type 1 Brazilian sequences using a bioinformatics unit established in Salvador, Bahia, Brazil, to give support to the viral epidemiology studies

The analysis of genetic data for human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus type 1 (HTLV-1) is essential to improve treatment and public health strategies as well as to select strains for vaccine programs. However, the analysis of large quantities of genetic data requires collaborative efforts in bioinformatics, computer biology, molecular biology, evolution, and medical science. The objective of this study was to review and improve the molecular epidemiology of HIV-1 and HTLV-1 viruses isolated in Brazil using bioinformatic tools available in the Laboratório Avançado de Sáude Pública (Lasp) bioinformatics unit. The analysis of HIV-1 isolates confirmed a heterogeneous distribution of the viral genotypes circulating in the country. The Brazilian HIV-1 epidemic is characterized by the presence of multiple subtypes (B, F1, C) and B/F1 recombinant virus while, on the other hand, most of the HTLV-1 sequences were classified as Transcontinental subgroup of the Cosmopolitan subtype. Despite the high variation among HIV-1 subtypes, protein glycosylation and phosphorylation domains were conserved in the pol, gag, and env genes of the Brazilian HIV-1 strains suggesting constraints in the HIV-1 evolution process. As expected, the functional protein sites were highly conservative in the HTLV-1 env gene sequences. Furthermore, the presence of these functional sites in HIV-1 and HTLV-1 strains could help in the development of vaccines that pre-empt the viral escape process.