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Nucleotide variants of the cancer predisposing gene CDH1 and the risk of non-syndromic cleft lip with or without cleft palate.

ABSTRACT: The CDH1 gene plays an important role during carcinogenesis and craniofacial morphogenesis. Germline mutations in this gene have been described in families presenting syndromic diffuse gastric cancer and orofacial clefts. The aim of this study was to evaluate the association between nucleotide variants of CDH1 and the risk of non-syndromic cleft lip with or without cleft palate (NSCL/P). Six single nucleotide polymorphisms (SNPs) of the CDH1 gene (rs16260, rs9929218, rs7186053, rs4783573, rs16958383, and rs1801552) were genotyped using the TaqMan SNP genotyping assays in 250 patients with NSCL/P and 540 controls from the Polish population. Comparison between patient and control groups showed that the CDH1 rs1801552 variant, under the assumption of recessive model, was associated with a two-fold decrease in the risk of NSCL/P (ORTT vs CT + CC = 0.481, 95 % CI 0.281-0.824, p = 0.007). This association remained statistically significant even after the multiple testing correction. No significant associations with NSCL/P risk were found for the other five tested SNPs. We found a strong association between the cancer predisposing gene CDH1 and the risk of NSCL/P in the Polish population. This result, together with previous observations of co-occurrence of orofacial clefts and a variety of cancer types, suggests the need for replication studies testing rs1801552 in NSCL/P cohorts with a known cancer history.

SUBMITTER: Hozyasz KK

PROVIDER: S-EPMC4164844 | biostudies-literature |

REPOSITORIES: biostudies-literature

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SATB2 gene variants in non-syndromic cleft lip with or without cleft palate in Indian population.

Project description:OBJECTIVES:Non-syndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common craniofacial birth defects and little is known about its aetiology. Initial studies of cytogenetic analysis provided the clues for possible genes involved in the pathogenesis of NSCL/P. This approach led to the identification of SATB2 gene on 2q32-q33. The aim of this study was to determine the association between SATB2 mutations and NSCL/P. MATERIALS AND METHODS:The rs137853127, rs200074373 and rs1992950 mutations of the SATB2 gene were investigated in 173 patients with NSCL/P and 176 normal controls using Kbioscience KASPar chemistry, which is a competitive allele-specific PCR SNP genotyping system. RESULTS:The mutations in exon 6 (rs137853127 and rs200074373) were monomorphic, the intronic variant (rs1992950) was polymorphic and genotype distribution was in agreement with Hardy-Weinberg equilibrium. The rs1992950 genotype distribution is not statistically significant between NSCL/P and controls. CONCLUSION:Our findings suggest that the SATB2 gene variations do not contribute to the development of NSCL/P in the south Indian population.

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Expression Quantitative Trait Locus Study of Non-Syndromic Cleft Lip with or without Cleft Palate GWAS Variants in Lip Tissues.

Project description:Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a complex disease with a strong genetic component. More than 40 loci have been identified to be associated with the risk of NSCL/P by genome-wide association studies (GWASs), but the majority of these variants are mapped to non-coding regions of the genome. Expression quantitative trait locus (eQTL) studies have increasingly been integrated with GWASs to identify target genes for these non-coding variants. In this study, we generated a unique, lip-specific eQTL dataset from 40 NSCL/P patients. A total of 5158 eQTL SNPs (eSNPs) -689 eQTL genes were identified after multiple corrections. Then, we integrated nominal eQTL SNPs with NSCL/P risk SNPs and identified 243 variants associated with the expression of 18 genes in lip tissues. Functional annotation analysis indicated that these risk eSNPs were significantly enriched in transcription regulation and chromatin open regions on the genome. These susceptible genes were enriched in cell fate determination, the pluripotency of stem cells, and Wnt signaling pathways. Finally, 8 of the 18 susceptible genes were differentially expressed in NSCL/P case-control studies. In summary, we have generated a unique lip-specific eQTL resource and identified multiple associations for NSCL/P risk loci, which should inform functional studies of NSCL/P biology.

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Non-syndromic Cleft Lip and Palate Polymorphisms Affect Normal Lip Morphology.

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| S-EPMC8756534 | biostudies-literature

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Project description:Rare coding variants are a current focus in studies of complex disease. Previously, at least 68 rare coding variants were reported from candidate gene sequencing studies in non-syndromic cleft lip and palate (NSCL/P), a common birth defect. Advances in sequencing technology have now resulted in thousands of sequenced exomes, providing a large resource for comparative genetic studies. We collated rare coding variants reported to contribute to NSCL/P and compared them to variants identified from control exome databases to determine if some might be rare but benign variants. Seventy-one percentage of the variants described as etiologic for NSCL/P were not present in the exome data, suggesting that many likely contribute to disease. Our results strongly support a role for rare variants previously reported in the majority of NSCL/P candidate genes but diminish support for variants in others. However, because clefting is a complex trait it is not possible to be definitive about the role of any particular variant for its risk for NSCL/P.

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