Mesothelin promoter variants are associated with increased soluble mesothelin-related peptide levels in asbestos-exposed individuals.

Autor:	De Santi C; Department of Biology, University of Pisa, Via Derna 1, Pisa, Italy., Pucci P; Department of Biology, University of Pisa, Via Derna 1, Pisa, Italy., Bonotti A; Preventive and Occupational Medicine, University Hospital of Pisa, Pisa, Italy., Melaiu O; Department of Biology, University of Pisa, Via Derna 1, Pisa, Italy., Cipollini M; Department of Biology, University of Pisa, Via Derna 1, Pisa, Italy., Silvestri R; Department of Biology, University of Pisa, Via Derna 1, Pisa, Italy., Vymetalkova V; Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Praha, Czech Republic., Barone E; Department of Biology, University of Pisa, Via Derna 1, Pisa, Italy., Paolicchi E; Department of Biology, University of Pisa, Via Derna 1, Pisa, Italy., Corrado A; Department of Biology, University of Pisa, Via Derna 1, Pisa, Italy., Lepori I; Department of Biology, University of Pisa, Via Derna 1, Pisa, Italy., Dell'Anno I; Department of Biology, University of Pisa, Via Derna 1, Pisa, Italy., Pellè L; Department of Biology, University of Pisa, Via Derna 1, Pisa, Italy., Vodicka P; Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Praha, Czech Republic., Mutti L; School of Environment and Life Sciences, University of Salford, Manchester, United Kingdom., Foddis R; Department of Translational Research and of new Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy., Cristaudo A; Department of Translational Research and of new Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy., Gemignani F; Department of Biology, University of Pisa, Via Derna 1, Pisa, Italy., Landi S; Department of Biology, University of Pisa, Via Derna 1, Pisa, Italy.
Jazyk:	angličtina
Zdroj:	Occupational and environmental medicine [Occup Environ Med] 2017 Jun; Vol. 74 (6), pp. 456-463. Date of Electronic Publication: 2017 Mar 25.
DOI:	10.1136/oemed-2016-104024
Abstrakt:	Background: Soluble mesothelin-related peptide (SMRP) is a promising diagnostic biomarker for malignant pleural mesothelioma (MPM), but various confounders hinder its usefulness in surveillance programmes. We previously showed that a single nucleotide polymorphism (SNP) within the 3'untranslated region (3'UTR) of the mesothelin ( MSLN ) gene could affect the levels of SMRP. Objectives: To focus on SNPs located within MSLN promoter as possible critical genetic variables in determining SMRP levels. Methods: The association between SMRP and SNPs was tested in 689 non-MPM subjects and 70 patients with MPM. Reporter plasmids carrying the four most common haplotypes were compared in a dual luciferase assay, and in silico analyses were performed to investigate the putative biological role of the SNPs. Results: We found a strong association between serum SMRP and variant alleles of rs3764247, rs3764246 (in strong linkage disequilibrium with rs2235504) and rs2235503 in non-MPM subjects. Inclusion of the genotype information led to an increase in SMRP specificity from 79.9% to 85.5%. Although not statistically significant, the group with MPM showed the same trend of association. According to the in vitro luciferase study, rs3764247 itself had a functional role. In silico approaches showed that the binding sites for transcription factors such as Staf and ZNF143 could be affected by this SNP. The other SNPs were shown to interact with each other in a more complex way. Conclusions: These data support the suggestion that SMRP performance is affected by individual (ie, genetic) variables and that MSLN expression is influenced by SNPs located within the promoter regulatory region. Competing Interests: Competing interests: None declared. (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
Databáze:	MEDLINE
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