Exploring GRHL3 polymorphisms and SNP-SNP interactions in the risk of non-syndromic oral clefts in the Brazilian population

Author(s)

Azevedo, Camilla de Marchi Sanches ^[1] ; Machado, Renato Assis ^[2] ; Martelli-Junior, Hercilio ^{[3, 4]} ; Reis, Silvia Regina de Almeida ^[5] ; Persuhn, Darlene Camati ^[6] ; Coletta, Ricardo D. ^[2] ; Rangel, Ana Lucia Carrinho Ayroza ^[1]

Affiliation

^[1] State Univ Western Parana, Sch Dent, Ctr Biol Sci & Hlth, BR-85819110 Cascavel, Parana - Brazil

^[2] Univ Estadual Campinas, Sch Dent, Dept Oral Diag, Piracicaba - Brazil

^[3] Univ Estadual Montes Claros, Stomatol Clin, Sch Dent, Montes Claros - Brazil

^[4] Univ Jose Rosario Vellano, Sch Dent, Ctr Rehabil Craniofacial Anomalies, Alfenas - Brazil

^[5] Bahiana Sch Med & Publ Hlth, Dept Basic Sci, Salvador, BA - Brazil

^[6] Univ Fed Paraiba, Mol Biol Dept, Joao Pessoa, Paraiba - Brazil

• Document type: Journal article
• Source: ORAL DISEASES; v. 26, n. 1, p. 145-151, JAN 2020.
• Web of Science Citations: 3

Abstract

Objective To investigate the association of single-nucleotide polymorphisms (SNP) in grainyhead-like 3 (GRHL3) and to verify its possible interactions with others genes responsible for craniofacial development in the risk of non-syndromic oral cleft (NSOC). Methods Applying TaqMan allelic discrimination assays, we evaluated GRHL3 SNPs (rs10903078, rs41268753, and rs4648975) in an ancestry-structured case-control sample composed of 1,127 Brazilian participants {[}272 non-syndromic cleft palate only (NSCPO), 242 non-syndromic cleft lip only (NSCLO), 319 non-syndromic cleft lip and palate (NSCLP), and 294 healthy controls]. Additionally, SNP-SNP interactions of GRHL3 and previously reported variants in FAM49A, FOXE1, NTN1, and VAX1 were verified in non-syndromic cleft lip with or without cleft palate (NSCL +/- P). To eliminate false-positive associations, Bonferroni correction or 1,000 permutation method was applied. Results The multiple logistic regression analysis showed that the CC genotype of rs10903078 (p = .03) and the haplotype C-C formed by the SNPs rs10903078 and rs41268753 (p = .04) were associated with NSCLO, but the p-values did not withstand Bonferroni correction. However, SNP-SNP test revealed significant interactions between GRHL3 SNPs and FAM49A (rs7552), FOXE1 (rs3758249), VAX1 (rs7078160 and rs751231), and NTN1 (rs9891446). Conclusions Our results confirm the importance of GRHL3 and its interactions with previously NSOC-associated genes, including FAM49A, FOXE1, NTN1, and VAX1, in the pathogenesis of NSOC in the Brazilian population. (AU)

• FAPESP's process: 16/02667-0 - Interactions Between Environment Factors and Polymorphic Variants in Genes Associated with Oxidative Stress in the Susceptibility of Nonsyndromic Oral Clefts
• Grantee: Ricardo Della Coletta
• Support Opportunities: Regular Research Grants