Association of <i>DVL2</i> and <i>AXIN2</i> gene polymorphisms with cleft lip with or without cleft palate in a polish population

Mostowska, Adrianna; Hozyasz, Kamil K.; Wójcicki, Piotr; Lasota, Agnieszka; Dunin-Wilczyńska, Izabella; Jagodzińśki, Paweł P.

doi:10.1002/bdra.23056

Cited by 22 publications

(25 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AXIN2 has been implicated in the etiology of NSOFCs in multiple populations, except Africans, with rs3923086 demonstrating an association with NSCLP among Asians (Letra et al 2012). Other studies (Mostowska et al 2012;de Araujo et al 2015) have replicated the association between AXIN2 and NSCL/P. Here, we have demonstrated that rs3923086 (AXIN2) is also associated with NSCLP among Africans in DFAM analyses.…”

Section: Discussionsupporting

confidence: 81%

Association Studies and Direct DNA Sequencing Implicate Genetic Susceptibility Loci in the Etiology of Nonsyndromic Orofacial Clefts in Sub-Saharan African Populations

et al. 2016

View full text Add to dashboard Cite

Orofacial clefts (OFCs) are congenital dysmorphologies of the human face and oral cavity, with a global incidence of 1 per 700 live births. These anomalies exhibit a multifactorial pattern of inheritance, with genetic and environmental factors both playing crucial roles. Many loci have been implicated in the etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in populations of Asian and European ancestries, through genome-wide association studies and candidate gene studies. However, few populations of African descent have been studied to date. Here, the authors show evidence of an association of some loci with NSCL/P and nonsyndromic cleft palate only (NSCPO) in cohorts from Africa (Ghana, Ethiopia, and Nigeria). The authors genotyped 48 single-nucleotide polymorphisms that were selected from previous genome-wide association studies and candidate gene studies. These markers were successfully genotyped on 701 NSCL/P and 163 NSCPO cases, 1,070 unaffected relatives, and 1,078 unrelated controls. The authors also directly sequenced 7 genes in 184 nonsyndromic OFC (NSOFC) cases and 96 controls from Ghana. Population-specific associations were observed in the casecontrol analyses of the subpopulations, with West African subpopulations (Ghana and Nigeria) showing a similar pattern of associations. In meta-analyses of the case-control cohort, PAX7 (rs742071, P = 5.10 × 10 -3 ), 8q24 (rs987525, P = 1.22 × 10 -3 ), and VAX1 (rs7078160, P = 0.04) were nominally associated with NSCL/P, and MSX1 (rs115200552, P = 0.01), TULP4 (rs651333, P = 0.04), CRISPLD2 (rs4783099, P = 0.02), and NOG1 (rs17760296, P = 0.04) were nominally associated with NSCPO. Moreover, 7 loci exhibited evidence of threshold overtransmission in NSOFC cases through the transmission disequilibrium test and through analyses of the family-based association for disease traits. Through DNA sequencing, the authors also identified 2 novel, rare, potentially pathogenic variants (p.Asn323Asp and p.Lys426IlefsTer6) in ARHGAP29. In conclusion, the authors have shown evidence for the association of many loci with NSCL/P and NSCPO. To the best of this knowledge, this study is the first to demonstrate any of these association signals in any African population.

show abstract

Section: Discussionsupporting

confidence: 81%

Association Studies and Direct DNA Sequencing Implicate Genetic Susceptibility Loci in the Etiology of Nonsyndromic Orofacial Clefts in Sub-Saharan African Populations

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The role of Dvl2 in the canonical Wnt signalling depends on its ability to form a platform for dynamic recruitment of Axin and other Wnt partners (43). It is interesting to note that in our previous studies we have showed that the AXIN2 nucleotide variants are risk factors for both non-syndromic tooth agenesis and orofacial clefts in the Polish population (29,44). Moreover, we have shown for the first time that polymorphisms of DVL2 are significantly associated with the susceptibility to NSCL/P (44).…”

Section: Discussionmentioning

confidence: 92%

Nucleotide variants of genes encoding components of the Wnt signalling pathway and the risk of non‐syndromic tooth agenesis

et al. 2012

View full text Add to dashboard Cite

Tooth agenesis is one of the most common dental anomalies, with a complex and not yet fully elucidated aetiology. Given the crucial role of the Wnt signalling pathway during tooth development, the purpose of this study was to determine whether nucleotide variants of genes encoding components of this signalling pathway might be associated with hypodontia and oligodontia in the Polish population. A set of 34 single nucleotide polymorphism (SNPs) in 13 WNT and WNT-related genes were analyzed in a group of 157 patients with tooth agenesis and a properly matched control group (n = 430). In addition, direct sequencing was performed to detect mutations in the MSX1, PAX9 and WNT10A genes. Both single-marker and haplotype analyses showed highly significant association between SNPs in the WNT10A gene and the risk for tooth agenesis. Moreover, nine pathogenic mutations within the coding region of the WNT10A gene were identified in 26 out of 42 (62%) tested patients. One novel heterozygous mutation was identified in the PAX9 gene. Borderline association with the risk of non-syndromic tooth agenesis was also observed for the APC, CTNNB1, DVL2 and WNT11 polymorphisms. In conclusion, nucleotide variants of genes encoding important components of the Wnt signalling pathway might influence the risk of tooth agenesis.

show abstract

“…The impact of the rs7210356 polymorphism in lip and palate development is unclear and our findings are of interest especially to understand this association. Haplotype analysis showed that five SNPs in AXIN2 (rs7591, rs7210356, rs4791171, rs11079571 and rs3923087) were associated with occurrence of NSCL ± P. Previously studies revealed that the both rs7591 and rs3923087 were associated with NSCL ± P and tooth agenesis [37, 46]. …”

Section: Discussionmentioning

confidence: 99%

“…Genotyping analyses were randomly repeated in 10% of the samples, and the concordance rate was 100%. These SNPs were selected based on their minor allele frequencies (www.ncbi.nlm.nih.gov) and because they were described as risk factors for oral cleft and breast and gastric cancer [29, 37, 39, 40, 43–46]. The study was approved by the ethics review board of each of the centers or hospitals affiliated with the collaborative study.…”

Section: Methodsmentioning

confidence: 99%

Clinical relevance of breast and gastric cancer-associated polymorphisms as potential susceptibility markers for oral clefts in the Brazilian population

et al. 2017

View full text Add to dashboard Cite

BackgroundEpidemiological studies have indicated a higher incidence of breast and gastric cancer in patients with nonsyndromic cleft lip with or without cleft palate (NSCL ± P) and their relatives, which can be based on similar genetic triggers segregated within family with NSCL ± P.MethodsThis multicenter study evaluated the association of 9 single nucleotide polymorphisms (SNP) in AXIN2 and CDH1, representing genes consistently altered in breast and gastric tumors, with NSCL ± P in 223 trios (father, mother and patient with NSCL ± P) by transmission disequilibrium test (TDT).ResultsOur results showed that the minor A allele of rs7210356 (p = 0.01) and the T-G-G-A-G haplotype formed by rs7591, rs7210356, rs4791171, rs11079571 and rs3923087 SNPs (p = 0.03) in AXIN2 were significantly under-transmitted to patients with NSCL ± P. In CDH1 gene, the C-G-A-A and A-G-A-G haplotypes composed by rs16260, rs9929218, rs7186053 and rs4783573 polymorphisms were respectively over-transmitted (p = 0.01) and under-transmitted (p = 0.008) from parents to the children with NSCL ± P.ConclusionsThe results suggest that polymorphic variants in AXIN2 and CDH1 may be associated with NSCL ± P susceptibility, and reinforce the putative link between cancer and oral clefts.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-017-0390-y) contains supplementary material, which is available to authorized users.

show abstract

Association of DVL2 and AXIN2 gene polymorphisms with cleft lip with or without cleft palate in a polish population

Abstract: This study suggests that polymorphic variants of the Wnt/β-catenin pathway genes have a role in the susceptibility to orofacial clefts. The DVL2 and AXIN2 genes might be candidate genes for this craniofacial anomaly in the Polish population. Birth Defects Research (Part A), 2012.

Cited by 22 publications

References 48 publications

Association Studies and Direct DNA Sequencing Implicate Genetic Susceptibility Loci in the Etiology of Nonsyndromic Orofacial Clefts in Sub-Saharan African Populations

Association Studies and Direct DNA Sequencing Implicate Genetic Susceptibility Loci in the Etiology of Nonsyndromic Orofacial Clefts in Sub-Saharan African Populations

Nucleotide variants of genes encoding components of the Wnt signalling pathway and the risk of non‐syndromic tooth agenesis

Clinical relevance of breast and gastric cancer-associated polymorphisms as potential susceptibility markers for oral clefts in the Brazilian population

Contact Info

Product

Resources

About