Evaluation of genome-wide association signals for nonsyndromic cleft lip with or without cleft palate in a multiethnic Brazilian population

To evaluate previous nonsyndromic cleft lip with or without cleft palate (NSCL±P) associated signals in 4p16.2, 8p11.23, 12q13.13, 12q13.2 and 17q21.32 in a multiethnic Brazilian cohort. The single nucleotide polymorphisms (SNPs) rs34246903 in 4p16.2, rs13317 in 8p11.23 (FGFR1, fibroblast growth fac...

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Published in:Archives of oral biology 2022-03, Vol.135, p.105372-105372, Article 105372
Main Authors: Machado, Renato Assis, Ayroza Rangel, Ana Lúcia Carrinho, de Almeida Reis, Silvia Regina, Scariot, Rafaela, Coletta, Ricardo D., Martelli-Júnior, Hercílio
Format: Article
Language:English
Subjects:
12q13.13
12q13.2
17q21.32
4p16.2
8p11.23
Alleles
Brazil
Case-Control Studies
Cleft Lip - genetics
Cleft Palate - genetics
FGFR1
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Nonsyndromic oral clefts
Polymorphism, Single Nucleotide
Receptor, Fibroblast Growth Factor, Type 1 - genetics
Risk factor
Single-nucleotide polymorphism
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Summary:To evaluate previous nonsyndromic cleft lip with or without cleft palate (NSCL±P) associated signals in 4p16.2, 8p11.23, 12q13.13, 12q13.2 and 17q21.32 in a multiethnic Brazilian cohort. The single nucleotide polymorphisms (SNPs) rs34246903 in 4p16.2, rs13317 in 8p11.23 (FGFR1, fibroblast growth factor receptor 1), rs3741442 in 12q13.13, rs705704 in 12q13.2 and rs4968247 in 17q21.32 were genotyped with TaqMan allelic discrimination assays in a case-control sample including 801 NSCL±P patients [233 nonsyndromic cleft lip (NSCLO) and 568 nonsyndromic cleft lip and palate (NSCLP)] and 881 healthy controls. Multiple logistic regression analyses, considering sex and genomic ancestry as covariates, were conducted, and the p value was adjusted with Bonferroni multiple correction testing (p ≤ 0.01). Although several associations were identified, those that resisted the multiple correction testing involved the alleles and genotypes of rs34246903 and rs13317. The NSCLO group had a lower frequency of the minor C allele of rs34246903 compared to controls, giving an odds ratio (OR) of 0.74 [95% confidence interval (CI): 0.59–0.93, p = 0.01]. The rs34246903 CC genotype (homozygous) and the recessive model revealed significant protective associations with NSCLO, yielding ORs of 0.50 (95% CI: 0.29–0.85, p = 0.005) and 0.55 (95% CI: 0.33–0.93, p = 0.01) respectively. The presence of C variant allele of rs13317 (OR: 0.81, 95% CI: 0.69–0.96, p = 0.01) as well the TC genotype (OR: 0.77, 95% CI: 0.62–0.94, p = 0.01) and the dominant model (OR: 0.77, 95% CI: 0.63–0.94, p = 0.009) showed significant associations with reduced risk of NSCL±P. Our study is the first to support the association of rs34246903 (4p16.2) with NSCLO and rs13317 within FGFR1 with NSCL±P in the highly admixed Brazilian population. Further studies are needed to determine the functionality of those SNPs or to identify the causal markers in linkage disequilibrium with those susceptibility markers. •Our study confirmed two previously polymorphisms reported with Brazilians.•The rs34246903 at locus 4p16.2 was associated with reduced risk of nonsyndromic cleft lip.•The rs13317 (FGFR1) reduced risk of nonsyndromic cleft lip with or without cleft palate.
ISSN:0003-9969
1879-1506
DOI:10.1016/j.archoralbio.2022.105372