RESUMO
OBJECTIVE: The study evaluated the association of BMP4 tag-SNPs and SNP-SNP interactions involving genes active by BMP4 pathway during craniofacial development in the susceptibility of nonsyndromic orofacial clefts (NSOC) in the Brazilian population. DESIGN: Case-control study. SETTING: Brazilian Oral Cleft Group. PARTICIPANTS: The study included 881 healthy controls and 800 patients with different types of NSOC: 232 with cleft lip only (NSCLO), 568 with cleft lip and palate (NSCLP), and 274 with cleft palate only (NSCPO). INTERVENTIONS: The genomic DNA was genotyped with allelic discrimination assays for five BMP4 tag-SNPs (rs11623717, rs17563, rs2071047, rs2761887 and rs4898820), and analyzed their allelic and genotypic associations using multiple logistic regression. The interactions of these variants with genes involved in the BMP4 signaling pathway, including FGFR1, GREM1, NOG, VAX1 and the 4p16.2 locus, were explored. MAIN OUTCOME MEASURES: BMP4 variants in the NSOC risk. RESULTS: Although only nominal p values were identified when the whole sample was considered, subgroup analysis including the patients with high African genomic ancestry showed significant associations of rs2761887 with risk for nonsyndromic cleft lip with or without cleft palate (NSCL ± P)[(ORhom: 2.16; 95% CI: 1.21-3.85; p = 0.01) and (ORrec: 2.05; 95% CI: 1.21-3.47; p = 0.006)]. Thirteen significant SNP-SNP interactions involving BMP4 and the SNPs at FGFR1, GREM1, NOG and VAX1 and at locus 4p16.2 for increased risk of NSCL ± P were identified. CONCLUSIONS: Our results demonstrate an increased risk of NSCL ± P in Brazilian individuals with enrichment of African ancestry in the presence of the BMP4 rs2762887 polymorphism, and reveal relevant genetic contribution of SNP-SNP epistatic interactions involving BMP4 variants to NSCL ± P risk.
RESUMO
OBJECTIVES: The purpose of this study was to evaluate the prevalence of taurodontism in patients with nonsyndromic cleft lip and palate (NSCLP) within a Brazilian population. STUDY DESIGN: The study was designed as an epidemiologic case-control single-center study. Three hundred eighty-eight patients were included: 88 had NSCLP, and 300 comprised the control group. The first and second permanent mandibular molars were included in this study. By using panoramic radiographs, taurodontism was categorized as mesotaurodontism, hypotaurodontism, and hypertaurodontism. RESULTS: Seventy patients (23.3%) from the control group and 36 patients (40.9%) from the case group presented taurodontism (P < .001). In the control group, 108 (9%) teeth showed taurodontism, whereas in the case group with cleft lip and palate (CLP), 64 (18.2%) teeth showed dental anomalies (P < .001). In both groups, most taurodontic teeth presented hypotaurodontism, followed by mesotaurodontism, while hypertaurodontism was found in only two teeth. The probability of taurodontism in patients with cleft lip (CL) was 2.36 (P = .010) times higher compared with those with CLP, whereas the occurrence of taurodontism in patients with cleft palate (CP) was 3.15 (P = .002) times greater than in patients with CLP. CONCLUSIONS: The results from this study indicate a close relationship between taurodontism and NSCLP and the possibility of different cleft subphenotypes.
