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Ethnic Differences in the Brazilian Population Influence the Impact of BMP4 Genetic Variants on Susceptibility of
Lilianny Querino Rocha de Oliveira1, Hellen Carolliny de Souza Nicolau1, Daniella Reis Barbosa Martelli2
1Graduate Program in Oral Biology, School of Dentistry, University of Campinas, Piracicaba, São Paulo, Brazil.
Summary
Genetic variants in BMP4 are associated with nonsyndromic orofacial clefts (NSOC) in Brazilians with African ancestry. Epistatic interactions between BMP4 and other genes also contribute to NSOC risk.
Area of Science:
- Genetics
- Developmental Biology
- Public Health
Background:
- Nonsyndromic orofacial clefts (NSOC) are common birth defects with complex etiology.
- The Bone Morphogenetic Protein 4 (BMP4) pathway plays a critical role in craniofacial development.
Purpose of the Study:
- To investigate the association of BMP4 tag single nucleotide polymorphisms (tag-SNPs) and their interactions with NSOC susceptibility in the Brazilian population.
- To explore SNP-SNP interactions involving BMP4 pathway genes in NSOC risk.
Main Methods:
- A case-control study was conducted with 800 NSOC patients and 881 healthy controls from the Brazilian Oral Cleft Group.
- Genotyping of five BMP4 tag-SNPs was performed, and associations were analyzed using multiple logistic regression.
- Interactions between BMP4 variants and SNPs in FGFR1, GREM1, NOG, VAX1, and the 4p16.2 locus were examined.
Main Results:
- Subgroup analysis revealed a significant association between BMP4 rs2761887 and increased risk for nonsyndromic cleft lip with or without cleft palate (NSCL±P) in individuals with high African genomic ancestry.
- Thirteen significant SNP-SNP interactions involving BMP4 and other genes (FGFR1, GREM1, NOG, VAX1, 4p16.2 locus) were identified, contributing to NSCL±P risk.
Conclusions:
- The BMP4 rs2761887 polymorphism is associated with an increased risk of NSCL±P in Brazilian individuals with African ancestry.
- Epistatic interactions between BMP4 variants and other genes significantly contribute to the genetic susceptibility of NSCL±P.
Keywords:
African ancestrySNP-SNP interactionsbone morphogenetic protein 4nonsyndromic orofacial cleftsMore Related Videos
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