Associação de polimorfismos no gene GRHL3 com fissuras de lábio e/ou palato não-sindrômicas em uma população brasileira

Abstract

Cleft lip and palate (CLP) are the most common craniofacial congenital malformations, which may be associated or not with syndromes. The etiology of the CLPs, although not fully elucidated, includes environmental, genetic factors and their interactions. In an attempt to clarify such a question, researches have investigated the genes associated with the syndromes with occurrence of cracks in their clinical spectrum, suggesting that the analysis of these same genes may extend to the group of non-syndromic oral clefts. This study aimed to determine the association of polymorphisms contained in the GRHL3 gene (Grainyhead-like 3) with susceptibility to the development of CL/P in non-syndromic individuals, since it plays an important role in the formation of the face, in addition to related to syndromic cases of oral clefts. For this purpose, a case-control approach was used with 833 cases of CL/PNS (non-syndromic cleft lip and/or palate), with 272 non-synchronous palatine fissure-CPNS, 242 non-sindromic cleft lip-CLNS and 319 non-synchronous cleft lip and palate- CLPNS and 294 controls, from 5 different regions of Brazil. The study was carried out from the collection of buccal cells obtained through mouthwash with sucrose solution 3%, in which, after DNA isolation, genomics ancestry tests were performed, as well as the genotyping of the SNPs rs 10903078, rs 41268753 and rs 4648975 in GRHL3, in order to investigate the existence of possible associations between these with the development of CL/PNS in a sample of the Brazilian population. There was predominance for European ancestry and a significant association between the rs10903078 SNP and CLNS was observed, however there were no associations between this and the other SNP when related to the other types of oral clefts. The logistic regression analysis showed that the homozygous CC genotype of rs10903078 was associated with CLNS (OR: 1.99; 95% CI: 0.83-1.78; p = 0.03), as well as the haplotype formed by the C-C alleles of the rs10903078 and rs41268753 SNPs presented an increased frequency in croup with CLNS (p = 0.04), although these associations were not significant after Bonferroni correction for multiple comparisons.