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Inverse correlation between HPSE gene single nucleotide polymorphisms and heparanase expression: possibility of multiple levels of heparanase regulation.

ABSTRACT: Heparanase is an endo-beta-glucuronidase that specifically cleaves the saccharide chains of heparan sulfate proteoglycans. Heparanase plays important roles in processes such as angiogenesis, tumor metastasis, tissue repair and remodeling, inflammation and autoimmunity. Genetic variations of the heparanase gene (HPSE) have been associated with heparanase transcription level. The present study was undertaken to identify haplotype or single nucleotide polymorphisms (SNPs) genotype combinations that correlate with heparanase expression both at the mRNA and protein levels. For this purpose, 11 HPSE gene SNPs were genotyped among 108 healthy individuals. Five out of the eleven polymorphisms revealed an association between the SNPs and heparanase expression. SNP rs4693608 exhibited a strong evidence of association. Analysis of haplotypes distribution revealed that the combination of two SNPs (rs4693608 and rs4364254) disclosed the most significant result. This approach allowed segregation of possible genotype combinations to three groups that correlate with low (LR: GG-CC, GG-CT, GG-TT, GA-CC), intermediate (MR: GA-CT, GA-TT) and high (HR: AA-TT, AA-CT) heparanase expression. Unexpectedly, LR genotype combinations were associated with low mRNA expressions level and high heparanase concentration in plasma, while HR genotype combinations were associated with high expression of mRNA and low plasma protein level. Because the main site of activity of secreted active heparanase is the extracellular matrix and cell surface, the origin and functional significance of plasma heparanase remain to be investigated. The current study indicates that rs4693608 and rs4364254 SNPs are involved in the regulation of heparanase expression and provides the basis for further studies on the association between HPSE gene SNPs and disease outcome.

SUBMITTER: Ostrovsky O

PROVIDER: S-EPMC2796676 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Inverse correlation between HPSE gene single nucleotide polymorphisms and heparanase expression: possibility of multiple levels of heparanase regulation.

Ostrovsky Olga O Korostishevsky Michael M Shafat Itay I Mayorov Margarita M Ilan Neta N Vlodavsky Israel I Nagler Arnon A

Journal of leukocyte biology 20090430 2

Heparanase is an endo-beta-glucuronidase that specifically cleaves the saccharide chains of heparan sulfate proteoglycans. Heparanase plays important roles in processes such as angiogenesis, tumor metastasis, tissue repair and remodeling, inflammation and autoimmunity. Genetic variations of the heparanase gene (HPSE) have been associated with heparanase transcription level. The present study was undertaken to identify haplotype or single nucleotide polymorphisms (SNPs) genotype combinations that ...[more]

PMID: 19406828

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Project description:BACKGROUND:FAS cell surface death receptor (FAS) gene has 2 common single nucleotide polymorphisms (SNPs) in its promoter, FAS-1377G?>?A (rs2234767) and FAS-670A?>?G (rs1800682). Several studies have investigated the role of these 2 polymorphisms in etiology of breast cancer in Asian population while the outcomes are inconsistent. To derive a more precise assessment of the association between breast cancer susceptibility with FAS gene promoter SNPs, a meta-analysis of published studies was performed. MATERIAL AND METHODS:We systematically searched PubMed, Embase, Web of Science, and the Chinese biomedical database (CBM) for papers published until November 1, 2018. Odds ratio (OR) with 95% confidential interval (95%CI) was conducted to evaluate the associations. Statistical analysis was conducted using Stata13.0 software. A total of 8 studies covering 2564 cases and 2633 controls were included. RESULTS:The integrated results suggest the following: For the FAS-1377G/A polymorphism, we only found significant associations for allele G vs allele A (OR?=?1.100, 95%CI?=?1.004-1.206, P?=?.040). After stratification by ethnicity, a significant association was observed only for the AA+GA vs GG genotype in East Asian populations (OR?=?1.177, 95% CI?=?1.010-1.371, P?=?.037). The association was not found in West Asian populations. For the FAS -670A/G polymorphism, no association with cancer risk was found in any comparison model. Sensitivity analysis suggests that the meta-analysis results obtained after excluding any single study were similar to the original ones, suggesting that the meta-analysis results were not significantly affected by any single study. CONCLUSION:These results indicated that FAS-1377G/A polymorphism may contribute to the increased breast cancer susceptibility and could be a promising target for cancer risk prediction. Further studies are needed to determine if the FAS gene confers a risk of breast cancer in other ethnic groups, such as Africans and Latin Americans.

Dataset Information

Inverse correlation between HPSE gene single nucleotide polymorphisms and heparanase expression: possibility of multiple levels of heparanase regulation.

Publications

Inverse correlation between HPSE gene single nucleotide polymorphisms and heparanase expression: possibility of multiple levels of heparanase regulation.

Similar Datasets

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