Polymorphisms at Regions 1p22.1 (rs560426) and 8q24 (rs1530300) Are Risk Markers for Nonsyndromic Cleft Lip and/or Palate in the Brazilian Population

Bagordakis, Elizabete; Paranaíba, Lívia Máris Ribeiro; Brito, Luciano Abreu; Aquino, Sibele Nascimento de; Messetti, Ana Camila; Martelli‐Júnior, Hercílio; Swerts, Mário Sérgio Oliveira; Graner, Edgard; Passos‐Bueno, Maria Rita; Coletta, Ricardo D.

doi:10.1002/ajmg.a.35830

Cited by 35 publications

(36 citation statements)

References 18 publications

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“…Thus, as part of the multistep approach in the identification of polymorphism‐disease associations, the first stage after GWAS involves replication studies with independent samples aiming the characterization of the true‐positive associations. Interestingly, in previous studies we confirmed the association of markers discovered by GWAS, such as 1p22.1 and 8q24 loci, with NSCL/P susceptibility in the Brazilian population (Brito et al, ; Bagordakis et al, ), but the involvements of 1q32.2, 10q25 and 20q12 in NSCL/P pathogenesis were not observed (Paranaíba et al, ; Bagordakis et al, ). The aim of this study was to verify the association of the NSCL/P susceptibility markers at regions 1p36 (rs742071), 2p21 (rs7590268), 3p11.1 (rs7632427), 8q21.3 (rs12543318), 13q31.1 (rs8001641), 15q22.2 (rs1873147), and 17q22 (rs227731) in the Brazilian population.…”

Section: Introductionsupporting

confidence: 77%

Analysis of susceptibility polymorphisms for nonsyndromic cleft lip with or without cleft palate in the Brazilian population

Aquino

Messetti

Hoshi

et al. 2014

Birth Defects Research

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Background: Although genome‐wide association studies have identified several susceptibility loci for nonsyndromic cleft lip with or without cleft palate (NSCL/P) in populations around the world, the role of most loci is unknown in the highly heterogeneous Brazilian population. Methods: To determine the association of 7 markers that showed genome‐wide significant association in Brazilians with NSCL/P, we conducted a structured association study conditioned upon the individual ancestry proportions to evaluate markers at 1p36 (rs742071), 2p21 (rs7590268), 3p11.1 (rs7632427), 8q21.3 (rs12543318), 13q31.1 (rs8001641), 15q22.2 (rs1873147), and 17q22 (rs227731) in 505 patients with NSCL/P and 594 healthy controls recruited from 2 different geographical regions of Brazil. The polymorphisms were genotyped by TaqMan 5′‐exonuclease allelic discrimination assay, and each sample was independently typed for 40 biallelic short insertion/deletion markers to characterize the genomic ancestry. Results: After Bonferroni correction for multiple tests, significant associations with NSCL/P were observed for rs742071, rs1873147, and rs227731. However, the frequency of the risk alleles varied between the geographical regions, according to the proportions of European and African genomic ancestry. The group enriched by European ancestry showed significant association with rs227731 (p = 0.001), whereas the group with high African ancestry was significantly associated with rs1873147 polymorphism (p = 0.005). The significant association with rs742071 was only detected in the combined sample (p = 0.005). Conclusion: The findings of the present study revealed the associations of 1p36 (rs742071), 15q22 (rs1873147), and 17p22 (rs227731) with NSCL/P in the Brazilian population, and further confirmed that the genetic heterogeneity of NSCL/P may be related to the different ethnic background of the affected individuals. Birth Defects Research (Part A) 100:36–42, 2014. © 2013 Wiley Periodicals, Inc.

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Section: Introductionsupporting

confidence: 77%

Analysis of susceptibility polymorphisms for nonsyndromic cleft lip with or without cleft palate in the Brazilian population

Aquino

Messetti

Hoshi

et al. 2014

Birth Defects Research

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“…However, later studies lacked to confirm this association in populations from China [32] and Brazil [33]. As an intergenic region, it is unknown whether markers at 10q25.3 are the cause of the association or are in linkage disequilibrium with adjacent causal variants in the genes.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in FGF12, VCL, CX43 and VAX1in Brazilian patients with nonsyndromic cleft lip with or without cleft palate

et al. 2013

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BackgroundNonsyndromic cleft lip with or without cleft palate (NSCL/P) is the most common orofacial birth defect with a wide range prevalence among different populations. Previous association studies with populations from Europe and Asia have identified putative susceptibility markers for NSCL/P in fibroblast growth factor 12 (FGF12), vinculin (VCL), connexin 43 (CX43) and in a region close to the ventral anterior homeobox 1 (VAX1) gene. However, there have thus far been no studies of these markers in NSCL/P Brazilian patients, and as the genetic ancestry of the Brazilian population is highly varied, the predisposition to those disease markers can be different.MethodsHerein we conducted a structured association study conditioned on the individual ancestry proportions to determine the role of 16 polymorphic markers within those genes in 300 patients with NSCL/P and 385 unaffected controls.ResultsNone of the alleles and genotypes showed association with NSCL/P, though there was a significant association of the haplotype formed by VAX1 rs10787760, rs6585429 and rs1871345 polymorphisms with NSCL/P that did not persist Bonferroni correction for multiple tests.ConclusionsOur results are consistent with a lack of involvement of FGF12, VCL and CX43 variants with NSCL/P pathogenesis in Brazilian patients. Furthermore, the higher frequency of a haplotype of VAX1 with NSCL/P patients suggests a low penetrant gene for oral cleft, and warrants further studies.

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“…Therefore, the present study was undertaken to determine the susceptibility of those polymorphisms as risk factors for NSCL/P in the Brazilian population, assessing the alleles and genotypes of the affected patients through TDT and case–control structured analysis. As the Brazilian population is result of the genetic admixture of three main ancestral populations (Europeans, Africans, and Amerindians) and displays very high levels of genomic diversity (Pena et al, ), we have previously demonstrated that the use of ancestry markers in association studies of ethnically mixed populations (structuration of the samples) is important to avoid interpretation bias (Brito et al, ; Bagordakis et al, ; de Aquino et al, ). In the present study, we confirmed the significant association of the polymorphism rs2274976 with NSCL/P etiology, but not with rs2236225.…”

Section: Discussionmentioning

confidence: 99%

MTHFR rs2274976 polymorphism is a risk marker for nonsyndromic cleft lip with or without cleft palate in the Brazilian population

Aquino

Hoshi

Bagordakis

et al. 2013

Birth Defects Research

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1Background: Polymorphisms within the MTHFR (rs2274976) and MTHFD1 (rs2236225) genes were previously associated with maternal susceptibility for having an offspring with nonsyndromic cleft lip with or without cleft palate (NSCL/P) in the Brazilian population. However, as the genotypes of the patients with NSCL/P were not evaluated, it is not clear whether the effects are associated with maternal or offspring genotypes. The aim of this study was to evaluate the association of rs2274976 and rs2236225 in the pathogenesis of NSCL/P. Methods: By using the TaqMan 5 0 -exonuclease allelic discrimination assay, the present study genotyped the rs2274976 and rs2236225 polymorphisms in 147 case-parent trios, 181 isolated samples of NSCL/P and 478 healthy controls of the Brazilian population. Transmission disequilibrium test and structured case-control analysis based on the individual ancestry proportions were performed. Results: The transmission disequilibrium test showed a significant overtransmission of the rs2274976 A allele (p 5 0.004), but no preferential parent-of-origin transmission was detected. The structured case-control analysis supported those findings, revealing that the minor A allele of rs2274976 was significantly more frequent in NSCL/P group compared with control group (p 5 0.001), yielding an odds ratio of 3.46 (95% confidence interval, 2. 05-5.85). No association of rs2236225 polymorphism with NSCL/P was observed in both transmission disequilibrium test and case-control analysis. Conclusion: The results of the study revealed that the presence of the rs2274976 A allele is a risk marker for the development of NSCL/P in the Brazilian population.Birth Defects Research (Part A) 100:30-35, 2014.

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Polymorphisms at Regions 1p22.1 (rs560426) and 8q24 (rs1530300) Are Risk Markers for Nonsyndromic Cleft Lip and/or Palate in the Brazilian Population

Cited by 35 publications

References 18 publications

Analysis of susceptibility polymorphisms for nonsyndromic cleft lip with or without cleft palate in the Brazilian population

Analysis of susceptibility polymorphisms for nonsyndromic cleft lip with or without cleft palate in the Brazilian population

Polymorphisms in FGF12, VCL, CX43 and VAX1in Brazilian patients with nonsyndromic cleft lip with or without cleft palate

MTHFR rs2274976 polymorphism is a risk marker for nonsyndromic cleft lip with or without cleft palate in the Brazilian population

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