Polymorphisms in the putative micro-RNA-binding sites of mesothelin gene are associated with serum levels of mesothelin-related protein.
BACKGROUND
Serum mesothelin, also known as soluble mesothelin-related protein (SMRP), reportedly shows increased levels in epithelial-type malignant pleural mesothelioma, but sometimes also arrives at high values in healthy asbestos-exposed subjects.


OBJECTIVE
This study aimed to investigate whether single nucleotide polymorphisms in the 3'untranslated region (3'UTR) of the mesothelin-encoded gene (MSLN) are associated with the SMRP levels measured in serum.


METHODS
The 3'UTR of the mesothelin gene was genotyped in 59 healthy asbestos-exposed subjects, selected on the basis of their SMRP levels. Direct sequencing did not show any new polymorphism, but enabled us to genotype two known SNPs (rs1057147, rs57272256). Differences in the mean values of SMRP in wild-type and variant heterozygote groups were calculated.


RESULTS
High levels of SMRP in healthy asbestos-exposed subjects were significantly associated with polymorphism rs1057147 (G<A). Regarding rs57272256, there was no statistically significant difference between wild-type and heterozygote groups. Our study suggests that rs1057147 polymorphism can affect mesothelin expression. Although these data need to be confirmed with a larger number of cases, this study warrants further research in order to better understand the relationship between mesothelin polymorphisms and SMRP.
Cristaudo
Alfonso
A
Department of Endocrinology and Metabolism, Orthopaedics and Traumatology, Occupational Medicine, University of Pisa, via Paradisa, 2 Pisa 56124, Italy. a.cristaudo@med.unipi.it
Foddis
Rudy
R
Bonotti
Alessandra
A
Simonini
Silvia
S
Vivaldi
Agnese
A
Guglielmi
Giovanni
G
Bruno
Rossella
R
Landi
Debora
D
Gemignani
Federica
F
Landi
Stefano
S
D001194:Asbestos / Q000633:toxicity; D001195:Asbestosis / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood; D058851:GPI-Linked Proteins; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000235:genetics*; D000090204:Mesothelin; D008654:Mesothelioma / Q000097:blood; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D009784:Occupational Diseases / Q000097:blood; D016273:Occupational Exposure / Q000009:adverse effects; D010997:Pleural Neoplasms / Q000097:blood; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011795:Surveys and Questionnaires
D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; C000715527:MSLN protein, human; D008562:Membrane Glycoproteins; D035683:MicroRNAs; D001194:Asbestos; D000090204:Mesothelin