A fissura labiopalatina é a anomalia craniofacial mais comum nos seres humanos e em relação à cavidade bucal a agenesia dentária se apresenta mais prevalente em indivíduos com fissuras labiopalatinas do que na população em geral. Esses fenótipos têm sido considerados decorrentes de alterações do desenvolvimento embrionário e ocorrem como resultado da interação de fatores genéticos e ambientais, caracterizando uma etiologia multifatorial. Tem sido apontado que a função anormal de alguns genes que possuem papel na formação craniofacial e dentária poderia estar relacionada à etiologia desses fenótipos. Dentre os genes candidatos para esses fenótipos têm se destacado o MSX1 entre outros. Dessa forma, o objetivo do trabalho foi avaliar a associação entre o polimorfismo no gene MSX1 (rs12532) com os fenótipos fissura labiopalatina e agenesia dentária não sindrômicos isolados ou em associação. A amostra foi composta por 222 indivíduos divididos em 4 grupos: grupo 1, indivíduos com fissura e agenesia dentária; grupo 2, indivíduos com fissura sem agenesia dentária; grupo 3, indivíduos com agenesia dentária sem fissura e grupo 4, controle (sem agenesia e sem fissura). Foi realizada a extração do DNA genômico a partir da saliva coletada dos indivíduos. O polimorfismo no gene MSX1 (rs12532) foi estudado por meio de Reação em cadeia da Polimerase em tempo real (PCR Real Time) utilizando o ensaio Taqman (Applied Biosystems). O teste do qui-quadrado (p<0,05) e o cálculo da razão de chances (IC=95%) foram utilizados na análise estatística. O polimorfismo no gene MSX1 esteve associado aos indivíduos dos grupos com agenesia associada à fissura e agenesias isoladas, porém não houve associação para os indivíduos do grupo com fissuras isoladas. Os resultados sugerem que o polimorfismo no gene MSX1 (rs12532) exerce um papel na suscetibilidade das agenesias dentárias na população brasileira em indivíduos com e sem fissura. / Cleft lip and palate is the most common craniofacial anomaly in humans and, in relation to oral cavity, tooth agenesis is significantly more prevalent in individuals with cleft lip and palate than in the general population. Cleft lip and palate and tooth agenesis phenotypes are considered changes in embryonic development and occur as a result of interaction between environmental and genetic factors, featuring a multifactorial etiology. It has been suggested that abnormal function of some genes that have role in craniofacial and tooth formation, could be related in the etiology of these phenotypes. Among the candidate genes for these phenotypes, MSX1 has been highlighted. The aim of this study was to investigate the association between the MSX1 gene polymorphism (rs12532) with nonsyndromic cleft lip and palate and tooth agenesis phenotypes isolated or in association. The sample was comprised of 222 individuals divided into 4 groups: group 1, cleft lip and palate with tooth agenesis; group 2, cleft lip and palate without tooth agenesis; group 3, tooth agenesis without cleft and group 4, a control group without tooth agenesis or cleft. Genomic DNA extraction was performed from the saliva collected from the individuals. The MSX1 gene polymorphism (rs 12532) was studied using real time PCR, Taqman method. The chi-square (p< 0.05) and odds ratio tests (CI= 95%) were performed for statistical analyses. The MSX1 polymorphism was associated with cleft lip and palate with tooth agenesis and isolated tooth agenesis groups, but no association was found between the polymorphism and isolated cleft lip and palate group. This suggests that MSX1 gene polymorphism (rs12532) plays a role in the susceptibility for tooth agenesis in the Brazilian population with and without cleft lip and palate.

Indiana University-Purdue University Indianapolis (IUPUI) / Purpose of the Study: Determine if there is an association of the CII/D2 malocclusion and genes linked to hypodontia, namely PAX9 and MSX1. Methods and Materials: One hundred probands with CII/D2 and one hundred non-CII/D2 with no hypodontia were enrolled in this study. Clinical exam, photographs, models, radiographs, and saliva were gathered. DNA was isolated from the saliva and sent for genetic analysis. Single Nucleotide Polymorphisms (SNPs) from the PAX9 and MSX1 genes were analyzed using the LightCycler® 480 to verify the presence of each with the CII/D2 malocclusion. A Hardy-Weinberg test was used to screen for genotyping errors, then a chi-square test was used to evaluate the association of the SNP genotypes. A p-value of 0.05 was considered significant. Results: The Hardy-Weinberg test showed no significant differences between observed and expected counts thus we used them for association analysis. Chi-square analysis indicated no significant association between CII/D2 and the MSX1 rs3821949 and the PAX9 1955734 genotypes. Although a p-value of 0.06 for the PAX9 rs8004560 suggested association, it was considered a grey area and insufficient to conclude that there was significant association. Since the SNP PAX9 rs8004560 was insufficient, additional statistical analysis was also performed on the PAX9 rs8004560 genotype of the CII/D2 affected subjects reported to have hypodontia of any tooth including third molars and excluding third molars. A chi-square test yielded a p-value of 0.08 on the analysis of CII/D2 with hypodontia for any permanent tooth except third molars, which suggested association, but insufficient to conclude a significant association. All other analyses indicated a lack of association of the PAX9 rs8004560 SNP. Conclusions: There is no significant association of CII/D2 and the SNPs MSX1 rs3821949 and PAX9 rs1955734. There is a suggestion that there is an association of the SNP PAX9 rs8004560 and CII/D2. There is a suggestion that there is an association of SNP PAX9 rs8004560 and CII/D2 subjects with hypodontia of any tooth except third molars.