Dataset Information

VAV3 Gene Polymorphism Is Associated with Paget's Disease of Bone.

ABSTRACT:

Background and aims

Paget's disease of bone (PDB) is a focal bone disorder affecting the skeleton segmentally. The disease affects osteoclasts which increase in size, number, and activity. One of the etiopathogenic hypotheses is that the disease is genetic. It has been reported that Rho GEF Vav3 is an essential factor in the regulation of osteoclast function, and alteration of the VAV3 gene could influence the development of the disease. The aim of our study was to perform an association study between variants of the VAV3 gene and the risk of developing Paget's disease of bone.

Patients and methods

The genotypic and allelic distribution of the VAV3 c.892A>T/p.T298S (rs7528153) polymorphism was compared between a cohort of 238 Spanish subjects with PDB and a cohort of 253 healthy subjects.

Results

Our results indicated that individuals carrying the VAV3 rs7528153 TT genotype were at a significantly increased risk of developing PDB (p < 0.001, odds ratio [OR] = 3.15, 95% confidence interval [95% CI] = 1.77-5.61).

Conclusions

These results suggest that inheriting the VAV3 rs7528153 polymorphism is a likely susceptibility factor for developing Paget's disease of bone.

SUBMITTER: Usategui-Martin R

PROVIDER: S-EPMC4892207 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Publications

VAV3 Gene Polymorphism Is Associated with Paget's Disease of Bone.

Usategui-Martín Ricardo R Calero-Paniagua Ismael I García-Aparicio Judith J Corral-Gudino Luis L Del Pino Montes Javier J González Sarmiento Rogelio R

Genetic testing and molecular biomarkers 20160512 6

<h4>Background and aims</h4>Paget's disease of bone (PDB) is a focal bone disorder affecting the skeleton segmentally. The disease affects osteoclasts which increase in size, number, and activity. One of the etiopathogenic hypotheses is that the disease is genetic. It has been reported that Rho GEF Vav3 is an essential factor in the regulation of osteoclast function, and alteration of the VAV3 gene could influence the development of the disease. The aim of our study was to perform an association ...[more]

PMID: 27172236

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Project description:BackgroundHashimoto's thyroiditis (HT) is the most common form of autoimmune thyroid disease which leads, in most cases, to hypothyroidism. HT is also classified as a multifactorial disease, which is caused by an interaction between genetic and environmental factors. Current knowledge of HT genetics is still very limited, especially in Algerian population.ObjectiveWe wanted to investigate the association of two single-nucleotide polymorphisms (SNPs) inside VAV3 and SEPS genes with HT in Algerian population.MethodsWe conducted a case-control study that included 100 HT cases and 126 healthy controls that were recruited from three private endocrinology clinics. Two SNPs, rs7537605 and rs28665122 inside VAV3 and SEPS genes were genotyped using real-time polymerase chain reaction (real-time PCR). Binary logistic regression model was used to test the association of selected SNs with HT and linear regression model was used to test association of these SNPs with thyroid peroxidase antibodies (TPOAb) levels.ResultsBinary logistic regression results revealed no allelic association of the minor allele A between Hashimoto's thyroiditis cases and healthy controls (P=0.896) for the rs7537606 in VAV3 gene. The same observation was reported for the AA (P=0.477), AG (P=0.752) genotypes and for the genotypic models: dominant (P=1.0) and recessive (P=0.555). Also, there was no significant difference in the TT (P=0.230), TC (P=0.717) and allelic distribution of the minor allele T (P=0.859), and the combined models: TT + TC (P=1.0), TC + CC (P=0.138) between patients and controls for the rs28665122 polymorphism of the SEPS1 gene.ConclusionThis is the first genetic study that investigated the genetic association of rs7537605 and rs28665122 inside VAV3 and SEPS genes in Algerian population. Our results suggest that these two SNPs may not be involved in the pathogeneses of HT since we found no association between them and HT/TPOAb levels. Further research that will include larger sample size is required.

Project description:BackgroundThe bone is among the most frequently chosen sites for the metastatic spread of breast cancer. The prediction of biomarkers for BM (Bone Metastasis) and PDB (Paget's disease of bone) initiated from breast cancer could be critically important in categorizing individuals with a higher risk and providing targeted treatment for PDB and BM.AimsThis research aims to investigate the common key candidate biomarkers that contribute to BM-BCa (Bone metastasis of breast cancer) and PDB by employing network decomposition and functional enrichment studies.Methods and resultsThis research analyzed high-throughput transcriptome sequencing (RNA-Seq). For this work, the dataset (GSE121677) was downloaded from GEO (Gene Expression Omnibus), and DEGs were identified using Galaxy and R script 4.3. Using STRING (Search Tool for the Retrieval of Interacting Genes), high-throughput research created a protein-protein interaction network (PPIN). The BM-PDB-interactome was created using Cytoscape 3.9.1 and PDB biomarkers, with the top 3% DEGs from BM-BCa. Functional Enrichment Analysis (Funrich 3.1.3) and DAVID 6.8 performed functional and gene set enrichment analysis (GSEA) of putatively essential biomarkers. TCGA (The Cancer Genome Atlas) validated the discovered genes. Based on our research, we identified 1262 DEGs; among these DEGs, 431 genes were upregulated, and 831 genes were downregulated. During the third growth of the interactome, 20 more genes were pinned to the BM-PDB interactome. RAC2, PIAS1, EP300, EIF2S1, and LRP6 are among the additional 25% of genes identified to interact with the BM-PDB interactome. To corroborate the findings of the research presented, additional functional and gene set enrichment analyses have been performed.ConclusionOf the five reported genes (RAC2, PIAS1, EP300, EIF2S1, and LRP6), RAC2 was identified to function as the common key potential biomarker in the BM-PDB interactome analysis and validated by TCGA in the study presented.

Dataset Information

VAV3 Gene Polymorphism Is Associated with Paget's Disease of Bone.

Background and aims

Patients and methods

Results

Conclusions

Publications

VAV3 Gene Polymorphism Is Associated with Paget's Disease of Bone.

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