Sibele Nascimento de Aquino

Maternal polymorphisms in folic acid metabolic genes are associated with nonsyndromic cleft lip and/or palate in the Brazilian population

BACKGROUND Polymorphisms in genes that are involved in folic acid metabolism may be important maternal risk factors for the birth of a child with nonsyndromic cleft lip and/or palate (NSCL/P). The aim of this study was to determine the involvement of polymorphic variants in four genes (MTHFR, MTHFD1, MTR, and SLC19A1) that encode proteins related to folic acid metabolism in the women with susceptibility for having a child with NSCL/P. METHODS DNA samples from 106 mothers of children with NSCL/P (case group) and from 184 mothers of healthy children (control group) were genotyped by polymerase chain reaction associated with restriction fragment length polymorphism (PCR-RFLP). RESULTS One of 29 polymorphisms was associated with significantly increased maternal risk for NSCL/P. Mothers exhibiting the A variant allele (GA genotype) of the MTHFR rs2274976 polymorphism demonstrated a ~6 times increased risk for having a child with NSCL/P compared to G allele carriers (OR, 5.76; 95% CI, 3.32-9.99, p = 0.000001). Among mothers who did not use vitamins, the OR of NSCL/P was increased to 8.34 (95% CI, 3.75-18.55, p = 0.000001) in the presence of the GA genotype of the MTHFR rs2274976 polymorphism compared to those with the GG genotype. Gene-gene interaction analysis showed that the combination of MTHFR rs2274976, MTHFD1 rs2236225, and SLC19A1 rs1051266 was the best model for prediction of maternal risk for NSCL/P. CONCLUSION The findings of the present study suggested that genetic variants of folic acid metabolic genes may modulate maternal susceptibility for having an offspring with NSCL/P.

Polymorphisms at Regions 1p22.1 (rs560426) and 8q24 (rs1530300) Are Risk Markers for Nonsyndromic Cleft Lip and/or Palate in the Brazilian Population

Polymorphisms at Regions 1p22.1 (rs560426) and 8q24 (rs1530300) Are Risk Markers for Nonsyndromic Cleft Lip and/or Palate in the Brazilian Population Elizabete Bagordakis, L ivia M aris Ribeiro Paranaiba, Luciano Abreu Brito, Sibele Nascimento de Aquino, Ana Camila Messetti, Herc ilio Martelli-Junior, Mario Sergio Oliveira Swerts, Edgard Graner, Maria Rita Passos-Bueno, and Ricardo D. Coletta* Department of Oral Diagnosis, School of Dentistry, State University of Campinas, Piracicaba, S~ao Paulo, Brazil Stomatology Clinic, Dental School, State University of Montes Claros, Montes Claros, Minas Gerais, Brazil Human Genome Research Center, Institute of Biosciences, University of S~ao Paulo, S~ao Paulo, Brazil Center for Rehabilitation of Craniofacial Anomalies, Dental School, University of Jos e Ros ario Vellano, Minas Gerais, Brazil

Fissuras lábio palatinas não sindrômicas: relação entre o sexo e a extensão clínica

UNLABELLED Cleft lip and/or palate represent the most common congenital anomaly of the face. AIM To describe the correlation between non-syndromic cleft lip and/or palate and gender, and its severity in the Brazilian population. METHODS Cross-sectional study, between 2009 and 2011, in a sample of 366 patients. The data was analyzed with descriptive statistics and multinomial logistic regression with a 95% interval to estimate the likelihood of the types of cleft lip and/or palate affecting the genders. RESULTS Among the 366 cases of non-syndromic cleft lip and/or palate, the more frequent clefts were cleft lip and palate, followed respectively by cleft lip and cleft palate. The cleft palates were more frequent in females, while the cleft lip and palate and cleft lips only predominated in males. The risk of cleft li in relation the cleft palate was 2.19 times in males when compared to females; while the risk of cleft lip and palate in relation to cleft palate alone was 2.78 times in males compared to females. CONCLUSION This study showed that there were differences in the distribution of the non-syndromic cleft lip and/or palate between males and females.A fenda labial e/ou palatina representa a anomalia congenita mais comum na face. OBJETIVO: Descrever a correlacao existente entre a fenda labial e/ou palatina nao sindromica e genero e sua gravidade na populacao brasileira. METODO: Estudo transversal, conduzido entre 2009 e 2011, em uma amostra de 366 pacientes. Os dados foram analisados com estatistica descritiva e regressao logistica multinomial com intervalo de 95% para estimar a probabilidade dos tipos de fenda labial e/ou palatina afetar os generos. RESULTADOS: Entre os 366 casos de fenda labial e/ou palatina nao sindromica, as fendas mais frequentes foram a fenda labio-palatina, seguida, respectivamente, pela fenda labial e fenda palatina. As fendas palatinas foram mais frequentes entre as mulheres e a fenda labio-palatina e fenda labial apenas predominaram nos homens. O risco de fenda labial em relacao a fenda palatina foi de 2,19 vezes maior em homens quando comparados as mulheres; enquanto o risco de fenda labial e palatina em relacao a fenda palatina apenas foi 2,78 vezes em homens, quando comparados as mulheres. CONCLUSAO: Este estudo mostrou que ha diferencas na distribuicao de fendas labiais e/ou palatinas nao sindromicas entre homens e mulheres.

Polymorphisms in FGF12, VCL, CX43 and VAX1 in Brazilian patients with nonsyndromic cleft lip with or without cleft palate

BackgroundNonsyndromic cleft lip with or without cleft palate (NSCL/P) is the most common orofacial birth defect with a wide range prevalence among different populations. Previous association studies with populations from Europe and Asia have identified putative susceptibility markers for NSCL/P in fibroblast growth factor 12 (FGF12), vinculin (VCL), connexin 43 (CX43) and in a region close to the ventral anterior homeobox 1 (VAX1) gene. However, there have thus far been no studies of these markers in NSCL/P Brazilian patients, and as the genetic ancestry of the Brazilian population is highly varied, the predisposition to those disease markers can be different.MethodsHerein we conducted a structured association study conditioned on the individual ancestry proportions to determine the role of 16 polymorphic markers within those genes in 300 patients with NSCL/P and 385 unaffected controls.ResultsNone of the alleles and genotypes showed association with NSCL/P, though there was a significant association of the haplotype formed by VAX1 rs10787760, rs6585429 and rs1871345 polymorphisms with NSCL/P that did not persist Bonferroni correction for multiple tests.ConclusionsOur results are consistent with a lack of involvement of FGF12, VCL and CX43 variants with NSCL/P pathogenesis in Brazilian patients. Furthermore, the higher frequency of a haplotype of VAX1 with NSCL/P patients suggests a low penetrant gene for oral cleft, and warrants further studies.

Isolation and characterization of myofibroblast cell lines from oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) invasion is followed by several stromal events such as inflammatory and immune cell infiltration, neo-vascularization, fibroblast activation and occasionally myofibroblast emergence. Our previous studies demonstrated that myofibroblasts in the stroma of OSCC are associated with a more aggressive behavior, leading to shorter patient overall survival. Therefore, we evaluated whether OSCC-associated myofibroblasts have different characteristics compared to OSCC-associated fibroblasts. OSCC myofibroblast cell lines were isolated, cultured and characterized on the basis of the expression of specific isoform α of smooth muscle actin (α-SMA) and of the excessive production of type I collagen. To assess the proliferative potential of the cell lines, growth curves were constructed, whereas the production and activity of matrix metalloproteinases (MMP) were analyzed by ELISA and enzymography, respectively. Myofibroblast clones were positive for α-SMA and vimentin, and negative for pan-cytokeratin and CD34. In long time cultures, western blotting, flow cytometry and ELISA analysis revealed constant α-SMA expression and elevated production of type I collagen. There were no differences on proliferative potential between fibroblast and myofibroblast clones, but myofibroblast cells secreted significantly higher levels of MMP-1, -2, -9 and -13. Furthermore, MMP-2 gelatinolytic activity was significantly higher in myofibroblast clones. The results of this study suggest that myofibroblasts may contribute to OSCC invasion through elevation of MMP synthesis.

Contribution of polymorphisms in genes associated with craniofacial development to the risk of nonsyndromic cleft lip and/or palate in the Brazilian population.

Background and Objective: Nonsyndromic cleft lip and/or palate (NSCL/P) is a complex disease associated with both genetic and environmental factors. One strategy for identifying of possible NSCL/P genetic causes is to evaluate polymorphic variants in genes involved in the craniofacial development. Design: We carried out a case-control analysis of 13 single nucleotide polymorphisms in 9 genes related to craniofacial development, including TBX1, PVRL1, MID1, RUNX2, TP63, TGF?3, MSX1, MYH9 and JAG2, in 367 patients with NSCL/P and 413 unaffected controls from Brazil to determine their association with NSCL/P. Results: Four out of 13 polymorphisms (rs28649236 and rs4819522 of TBX1, rs7940667 of PVRL1 and rs1057744 of JAG2) were presented in our population. Comparisons of allele and genotype frequencies revealed that the G variant allele and the AG/GG genotypes of TBX1 rs28649236 occurred in a frequency significantly higher in controls than in the NSCL/P group (OR: 0.41; 95% CI: 0.25-0.67; p=0.0002). The frequencies of rs4819522, rs7940667 and rs1057744 minor alleles and genotypes were similar between control and NSCL/P group, without significant differences. No significant associations among cleft types and polymorphisms were observed. Conclusion: The study suggests for the first time evidences to an association of the G allele of TBX1 rs28649236 polymorphism and NSCL/P. Key words:Cleft lip, cleft palate, polymorphism, genetic.

Orofacial Features of Hypohidrotic Ectodermal Dysplasia

Hypohidrotic ectodermal dysplasia (HED) is a type of genodermatosis characterized by the abnormal development of sweat glands, teeth, and hair. The most prevalent form of HED is X-linked hypohidrotic ectodermal dysplasia (XLHED), which is associated with mutations in the EDA gene. The aim of this case report was to describe a family with XLHED with emphasis on differences in orofacial features between members. Family members were systematically evaluated to characterize the pattern of inheritance and clinical features. Dental examination included evaluation of agenesis and abnormal teeth structure. The pedigree of the last seven generations of the family was constructed. Clinical examination and medical history revealed five males affected by HED and nine female as heterozygous carriers. The males exhibited the classic phenotype of XLHED, with dental abnormalities, hypohydrosis, and craniofacial dysmorphologies. The heterozygous carriers of the X-linked gene defect principally exhibited dental agenesis of the lateral maxillary incisors. Careful clinical examination, including dental evaluation, is an important way to detect heterozygous carriers of X-linked HED. Heterozygous parents of patients with HED may also show some features of the disorder. The identification of female carriers results in genetic counseling being offered to affected families, as well as providing adequate treatment as necessary and long-term follow-up of these patients.

Interactions Between Rad51 Rs1801321 And Maternal Cigarette Smoking As Risk Factor For Nonsyndromic Cleft Lip With Or Without Cleft Palate

Interactions Between RAD51 rs1801321 and Maternal Cigarette Smoking as Risk Factor for Nonsyndromic Cleft Lip with or without Cleft Palate Renato Assis Machado, Helenara Salvati Bertolossi Moreira, Sibele Nascimento de Aquino, Hercilio Martelli-Junior, Silvia Regina de Almeida Reis, Darlene Camati Persuhn, Tao Wu, Yuan Yuan, and Ricardo D. Coletta* Department of Oral Diagnosis, School of Dentistry, State University of Campinas, Piracicaba, S~ao Paulo, Brazil Department of Physiotherapy, State University of Western Paran a, Paran a, Brazil Stomatology Clinic, Dental School, State University of Montes Claros, Montes Claros, Minas Gerais, Brazil Center for Rehabilitation of Craniofacial Anomalies, Dental School, University of Jos e Ros ario Vellano, Minas Gerais, Brazil Department of Basic Science, Bahiana School of Medicine and Public Health, Salvador, Bahia, Brazil Molecular Biology Department, Federal University of Paraı́ba, Jo~ao Pessoa, Paraı́ba, Brazil Peking University School of Public Health, Beijing, China

Oral and neurocutaneous phenotypes of familial tuberous sclerosis

OBJECTIVE The objective of this study was to describe the pattern of inheritance and the clinical features in a large family with tuberous sclerosis (TS), and to focus on the general diagnosis after the initial oral examination. STUDY DESIGN To characterize the pattern of inheritance and the clinical features, 61 familial members were systematically evaluated, including dermatologic, ophthalmologic, and orofacial examination. Imaging exams, such as abdomen ultrasonography, echocardiogram, fundoscopy, cranial cone-beam computerized tomography, and brain magnetic resonance, were performed. Hematoxylin and eosin stain and scanning electronic microscopy were performed to characterize TS-associated alterations in the teeth, nails, and hair. RESULTS The pedigree of the family was constructed including the 4 last generations and revealed nonconsanguineous marriages and an autosomal dominant mode of TS transmission. We identified 13 family members affected by TS, with 6 of them completely fulfilling the diagnostic criteria of this disorder. Hypomelanotic macules in the skin, facial angiofibromas, and dental enamel pits were the most common features of affected patients. Central nervous system alterations were identified in 5 family members, whereas cardiac and renal alterations were found in 1 member each. CONCLUSION We emphasize, in this study, the importance of oral findings such as dental enamel pits and gingival angiofibromas in the early diagnosis of familial TS which led to complete familial profile and pattern of inheritance establishment.

Prevalence of depressive symptoms in patients with cleft lip and palate.

INTRODUCTION Cleft lip and/or palate (CL/P) represent the most common congenital anomalies of the face. OBJECTIVE To evaluate the prevalence of depressive symptoms in children and adolescents with nonsyndromic cleft lip and/or palate (nsCL/P). METHODS We conducted an observational, case-control study, with a case study group composed of 61 patients with nsCL/P, aged 7-17 years, and a control group of 61 clinically normal patients. Both groups were selected at the same institution. RESULTS Depressive symptoms were observed in the case group (nsCL/P), but there were no statistically significant differences compared to the control group. No association was found between the two groups (case and control) in relation to sociodemographic variables: gender, age and education. CONCLUSIONS This study identified the prevalence of depressive symptoms in children and adolescents with nsCL/P from a localized geographic population, although the results were not statistically significant when compared to the control group, not justifying the use of CDI (Child Depression Inventory) as a screening instrument for depressive symptoms in the examined population.