O papel da epigenética na gênese das fissuras orofaciais

Abstract

Non-syndromic clefts of lip and/or palate (NSCL/P) are one of the most common congenital malformations at birth, which result from a failure in the development of the craniofacial structures of the embryo. They are characterized by the presence of a disruption in the normal characteristics of the mouth, and directly affect the quality of life and well-being of these patients, since essential functions for human development are impaired. With multifactorial etiology, it is the result of a complex interaction between genetic and environmental factors. Recent studies have shown that epigenetic processes, which are modulated by maternal behavior, are determinants in the morphogenesis of embryonic tissues, and changes in DNA methylation may be associated with the emergence of NSCL/P. In this scope, through the BRCA1 and LINE-1 biomarkers, was carried out the study of the specific and global DNA methylation pattern, respectively. Based on this, DNA extraction was performed from oral mucosa cells of 33 children with NSCL/P and 49 healthy children, followed by combined bisulfite restriction analysis. For LINE-1, polymerase chain reaction (PCR) was used followed by restriction enzymatic, and PCR methylation specific for BRCA1. Mothers also collaborated by answering a questionnaire to investigate the children's dietary profile and their exposure profile during pregnancy. The results suggest a greater tendency to global hypomethylation and hypermethylation in BRCA1 in children with clefts. The mean methylation of LINE-1 found was 48% and 45.3% between the control and cleft groups, respectively (p-value = 0.047), while for the BRCA1 promoter the value found was 30.4% and 56.5% in the controls and cleft, respectively, with no statistical difference between the groups. Both groups had a low quality dietary profile, but the diet was discretely better among the individuals in the cleft group. Low gestational programming rate was observed in addition to the time of contraceptive use before pregnancy being significantly higher for mothers in the cleft group (p-value = 0.036), being associated with an almost two times higher risk of NSCL/P (95% CI = 0.639 - 4.134). All these findings become relevant in elucidating the risk factors related to the development of this malformation.