Nonsyndromic cleft lip with or without cleft palate (NSCL ± P) is the most common orofacial birth defect, exhibiting variable prevalence around the world, often attributed to ethnic and environmental differences. Linkage analyses and genome-wide association studies have identified several genomic susceptibility regions for NSCL ± P, mostly in European-derived or Asian populations. Genetic predisposition to NSCL ± P is ethnicity-dependent, and the genetic basis of susceptibility to NSCL ± P likely varies among populations. The population of Brazil is highly admixed, with highly variable ancestry; thus, the genetic determinants of NSCL ± P susceptibility may be quite different. This study tested association of 8 single-nucleotide polymorphisms (SNPs), previously identified by genome-wide studies in other populations, with NSCL ± P in a Brazilian population with high African ancestry. SNPs rs560426, rs642961, rs1530300, rs987525, rs3758249, rs7078160, rs17085106, and rs13041247 were genotyped in 293 Brazilian patients with NSCL ± P and 352 unaffected Brazilian controls. Each sample was also genotyped for 40 biallelic short insertion/deletion polymorphic markers to characterize genetic ancestry. The average African ancestry background was 31.1% for the NSCL ± P group and 36.7% for the control group. After adjustment for ancestry and multiple testing, the minor alleles of rs3758249 (OR: 1.58, 95% CI: 1.25-2.01, P = 0.0001) and rs7078160 (OR: 1.59, 95% CI: 1.21-2.07, P = 0.0002) were significantly associated with risk of NSCL ± P. Polymorphisms located in IRF6 (rs642961) and 8q24 (rs1530300 and rs987525) showed marginal associations in this Brazilian population with high African ancestry. These results indicate that rs3758249 at 9q22 and rs7078160 at 10q25.3 represent risk loci for NSCL ± P in the Brazilian population with high African ancestry.
Background
GREM1, which encodes Gremlin 1, an antagonist of bone morphogenic proteins with effects on proliferation and apoptosis, has been considered a candidate gene for nonsyndromic cleft lip with or without cleft palate (NSCL±P). In this study, we investigated potential associations of single nucleotide polymorphisms (SNP) in GREM1 and NSCL±P risk in the Brazilian population. Additionally, SNP‐SNP interactions of GREM1 with previously reported rs1880646 variant in NTN1 (netrin 1), a gene also responsible for apoptotic phenotypes were verified.
Methods
Applying Taqman allelic discrimination assays, we evaluated the variants rs16969681, rs16969816, rs16969862, and rs1258763 in 325 case‐parent trios and in 1,588 isolated samples in a case‐control study. Allelic and genotypic analyses, as well as interaction tests assessing gene‐environmental factor (GxE) and SNP‐SNP interaction with rs1880646 variant in NTN1, were performed based on logistic regression analysis adjusted for the effects of gender and genomic ancestry proportions.
Results
The risk alleles of all SNP were undertransmitted in NSCL±P trios, though the case‐control analysis confirmed only the association with rs16969862 alleles (OR: 0.78, 95% CI: 0.63–0.96, p = .02). The GxE interaction analysis revealed a significant interaction between maternal environmental contact with agrotoxics and rs16969816 (OR: 0.25, 95% CI: 0.08–0.74, p = .01), and pairwise interaction test with NTN1 rs1880646 yielded significant p values in the 1,000 permutation test for rs16969681, rs16969816, and rs16969862.
Conclusion
The GREM1 is involved in the etiology of NSCL±P in the Brazilian population and reveal that the interaction between GREM1 and NTN1 may be related with the pathogenesis of this common craniofacial malformation.
| The non-syndromic cleft palate (NSCP) is a common congenital defect in humans. This work has aimed to perform a descriptive epidemiological study of patients with NSCP in the State of Bahia, Brazil. A questionnaire was applied to patients and/ or parents at three reference centres for treatment of craniofacial anomalies. Of the 135 patients with NSCP, 60% were female and 40% male. Blacks and mulattos were predominant. The most common systemic disorder was otologic findings. The average age of the surgery was 5 years and 2 months with a percentage of 74.8% operated. With regard to the mothers, 16.3 % consumed alcoholic beverages and 12.6 % smoked. The most cited vitamin supplementation was folic acid. Contact with chemicals involved 20.7 % of the fathers and 14.9 % of the mothers. The most frequent mother's age gestational ranged between 15 and 25 years old. The results showed that the frequency of children with NSCP in the State of Bahia is related to the location of the reference centres. Younger mothers gave birth to cleft palate children even despite using vitamin supplementation. Although no surgical procedure has been performed at an ideal age, the majority of the children with cleft palate were submitted to surgical repair.
jamento e implantação de programas de saúde bucal no local de trabalho, visando à promoção de saúde e prevenção de riscos.
Palavras-chave: Epidemiologia. Saúde bucal. Salva-vidas.
IntroduçãoA saúde de uma população sofre interferência de diversos fatores como a questão socioeconômica e cultural. Outro fator, que recebe cada vez mais importância é a questão ocupacional, uma vez que, no contexto da globalização e das inovações na economia, há um aumento das exigências dos trabalhadores, prejudicando a saúde e o rendimento¹. Com isso, surge a preocupação de promover serviços de saúde ao trabalhador, dando origem à concepção de saúde do trabalhador².A conscientização das classes trabalhadoras quanto à necessidade de tornar obrigatória a assistência à saúde do trabalhador para prevenir doenças levou esta discussão para a área odontológica³. A importância da saúde bucal para o alcance de padrões de boa qualidade de vida é evidente 4 .
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