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

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 discrimina...

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Bibliographic Details
Published in:Oral diseases 2020-01, Vol.26 (1), p.145-151
Main Authors: Azevedo, Camilla de Marchi Sanches, Machado, Renato Assis, Martelli‐Júnior, Hercílio, Reis, Silvia Regina de Almeida, Persuhn, Darlene Camati, Coletta, Ricardo D., Rangel, Ana Lúcia Carrinho Ayroza
Format: Article
Language:English
Subjects:
Brazil
Case-Control Studies
Cleft Lip - genetics
Cleft lip/palate
Cleft Palate - genetics
Craniofacial growth
Dentistry
DNA-Binding Proteins - genetics
FAM49A
Female
Forkhead Transcription Factors - genetics
FOXE1
Genetic Predisposition to Disease
Genotype
GRHL3
Haplotypes
Homeodomain Proteins - genetics
Humans
Intracellular Signaling Peptides and Proteins - genetics
Male
Netrin-1
Netrin-1 - genetics
non‐syndromic oral cleft
NTN1
Physical growth
Polymorphism, Single Nucleotide
risk factor
Single-nucleotide polymorphism
SNP‐SNP interaction
Transcription Factors - genetics
VAX1
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Summary: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.
ISSN:1354-523X
1601-0825
DOI:10.1111/odi.13204