Análise do perfil epigenético de crianças com fendas labiopalatinas não sindrômicas
Non-syndromic clefts of the lip and/or palate (NSCL/P) are birth defects arising from environmental and genetic causes. Recent studies have linked epigenetic factors, such as DNA methylation, to the inheritability of this complex malformation, as well as nutrition has been considered an environme...
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| Formato: | Dissertação |
| Idioma: | pt_BR |
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Brasil
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| Endereço do item: | https://repositorio.ufrn.br/jspui/handle/123456789/27808 |
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| Resumo: | Non-syndromic clefts of the lip and/or palate (NSCL/P) are birth defects arising from
environmental and genetic causes. Recent studies have linked epigenetic factors,
such as DNA methylation, to the inheritability of this complex malformation, as well as
nutrition has been considered an environmental trigger of NSCL/P acting directly on
the methylation profile. Thus, the aim of this work was to analyze the epigenetic
pattern of children with NSCL/P. The dietary pattern of oral clefts children and the
gestational exposure profile of their mothers were also investigated. Buccal mucosa
cells were collected from all children for DNA extraction and for global and specific
methylation determination. For this, the bisulfite restriction analysis (COBRA)
technique was performed to the 5-methylcytosines (5-mC) of LINE-1 and Alu regions
since they comprise about 30% of the human genome, in addition, the polymerase
chain reaction was performed to analyze the specific methylation of BRCA1
promoter. The choice of this gene was based on its role in genome stability. In
addition, the mothers collaborated answering a questionnaire about their exposure
factors during pregnancy and their children dietary information. As a result, the
control group showed a higher consumption of "ultraprocessed", "refined wheat",
"processed vegetable fats", "simple carbohydrates" and "sausages" (p <0.05), but for
the other food categories there was no statistical difference between groups.
Regarding the gestation data, a low gestational programming rate was observed and
consequent delay in the beginning of nutritional supplements use that support a
proper embryo development. In addition, contraceptive use time prior to gestation
was significantly higher for mothers in the clefts group and it was associated with a
nearly two-fold increased risk for non-syndromic oral clefts (p = 0.036, 95% CI=
0.639–4.134). About the global DNA methylation, it was found a mean LINE-1 5-mC
of 48% and 45.3% for control and clefts group, respectively, with significant statistical
difference (p = 0.047). The BRCA1 promoter was methylated in 30.4% and 56.5% of
control and clefts subjects, respectively, with no statistical difference between
groups. In general, it was seen a poor quality dietary profile of the research
participants and there was a higher tendency to global hypomethylation and BRCA1
hypermethylation in children with clefts. These findings corroborate with recent
speculations that DNA methylation may be the result of a transgenerational
epigenetic inheritance and it have effects on the etiology of this malformation. Further
studies are needed to confirm these findings and to understand other epigenetic
mechanisms that are acting in conjunction with the genetic susceptibility variants and
as a consequence of the environmental factors responsible for this phenotype
characterization. |
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