| Autor: |
Rocha de Oliveira, Lilianny Querino, de Souza Nicolau, Hellen Carolliny, Barbosa Martelli, Daniella Reis, Martelli-Júnior, Hercílio, Scariot, Rafaela, Ayroza Rangel, Ana Lúcia Carrinho, de Almeida Reis, Silvia Regina, Coletta, Ricardo D., Machado, Renato Assis |
| Zdroj: |
The Cleft Palate-Craniofacial Journal; October 2024, Vol. 61 Issue: 10 p1701-1712, 12p |
| Abstrakt: |
Objective The study evaluated the association of BMP4tag-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 BMP4tag-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 BMP4signaling pathway, including FGFR1, GREM1, NOG, VAX1and the 4p16.2 locus, were explored.Main outcome measures BMP4variants in the NSOC risk.Results Although only nominal pvalues 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 BMP4and the SNPs at FGFR1, GREM1, NOGand VAX1and 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 BMP4rs2762887 polymorphism, and reveal relevant genetic contribution of SNP-SNP epistatic interactions involving BMP4variants to NSCL ± P risk. |
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