Banca de QUALIFICAÇÃO: LUÍZA ARAÚJO DA COSTA XAVIER

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
DISCENTE: LUÍZA ARAÚJO DA COSTA XAVIER
DATA: 10/07/2015
HORA: 15:30
LOCAL: Sala de Reuniões do Instituto de Medicina Tropical - IMT/UFRN
TÍTULO:

Genome instability biomarkers and folic acid enzymes polymorphisms in children with non-syndromic cleft lip and/or palate

PALAVRAS-CHAVES:

Cleft lip palate, folic acid, single nucleotide polymorphism, micronuclei, genome instability

PÁGINAS: 16
GRANDE ÁREA: Ciências Biológicas
ÁREA: Genética
SUBÁREA: Genética Humana e Médica
RESUMO:

The non-syndromic cleft lip and/or palate (NSCLP) is a common birth defect caused by a combination of genetic and environmental factors. Studies have shown that genetic polymorphisms in enzymes regulating folic acid metabolism changes the availability of its byproducts, consequently impairing essential cellular functions, such as nucleotide synthesis and DNA repair. In addition, experiments also shows a causal association between folic acid deficiency and higher micronucleus frequency. Therefore, the aim of the present study is to evaluate the influence of folic acid enzymes polymorphisms on genome instability biomarkers and the association of these variables with NSCLP development in children from Northeast Brazil.  Fourty-eight patients with clefts and eighteen healthy children without clefts were recruited. Their genomic DNA was obtained to determine the polymorphisms in methylenetetrahydrofolate reductase (MTHFR; C677T and A1298C), methionine synthase (A2756C), methionine synthase reductase (A66G) and reduced folate carrier (RFC1; A80G) by PCR–RFLP, and to perform the cytokinesis-block micronucleus assay as instability biomarkers. The NSCLP patients had a higher frequency of micronucleus, nuclear buds (p < 0.001) and nucleoplasmic bridges (p = 0.001) than the control group. However, none of the polymorphisms evaluated modified significantly the biomarkers distribution. The logistic regression model reported that MTHFR (A1298C; p = 0.013), RFC1 (p = 0.001) and micronucleus (p = 0.043) were statistically significant to predict cleft phenotype. The high genome instability in children with oral clefts suggests a relevant role of DNA damage events and its corresponding response as a susceptibility factor in NSCLP development.

MEMBROS DA BANCA:
Externo ao Programa - 2323511 - ADRIANA AUGUSTO DE REZENDE
Externo ao Programa - 045.306.274-11 - MARCELA ABBOTT GALVÃO URURAHY - UFRN
Presidente - 350647 - SELMA MARIA BEZERRA JERONIMO