Polymorphisms in the putative micro-RNA-binding sites of mesothelin gene are associated with serum levels of mesothelin-related protein

Our plain-English summary of Polymorphisms in the putative micro-RNA-binding sites of mesothelin gene are associated with serum levels of mesothelin-related protein, by A. Cristaudo, R. Foddis, A. Bonotti, et al (Occupational and Environmental Medicine, 2010).

The study

• Authors: A. Cristaudo, R. Foddis, A. Bonotti, S. Simonini, A. Vivaldi, G. Guglielmi, R. Bruno, D. Landi, F. Gemignani, S. Landi
• Journal: Occupational and Environmental Medicine
• Published: 2010;67(4):233-6
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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.

Objectives: 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.

In plain English

This study asked whether inherited differences in the mesothelin gene relate to blood levels of soluble mesothelin-related protein (SMRP). SMRP has been proposed as a marker for malignant pleural mesothelioma, but it is sometimes high in healthy asbestos-exposed people. The authors studied 59 healthy men in Pisa, Italy, with past job exposure to asbestos and no pleural plaques. Of these, 21 had SMRP above 1 nM and 38 at or below 1 nM. The article did not report which asbestos fiber types the participants were exposed to. Two known gene variants were found. For rs1057147, 18 men carried the A variant. Their mean SMRP was 1.11 nM versus 0.80 nM in the 41 non-carriers, a statistically significant difference (p = 0.016). For rs57272256, the 8 carriers averaged 1.10 nM versus 0.86 nM in non-carriers, not statistically significant (p = 0.18). The authors said there were too few carriers for adequate statistical power. Computer predictions suggested 18 microRNAs might bind at the rs1057147 site. The authors concluded that genetic variation may partly explain raised SMRP in healthy people. They said the small study needs confirmation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Genetic association study comparing healthy asbestos-exposed subjects with higher versus lower serum SMRP levels. Subjects with SMRP above 1 nM were matched for age and gender with subjects at or below 1 nM. Gene sequencing was combined with computer-based (in silico) prediction of microRNA binding sites.
• Who was studied: 59 healthy, unrelated Caucasian men with a history of occupational asbestos exposure, enrolled at the University Hospital of Pisa, Italy, living along the north Tirrenian coast. People with previous or current neoplastic or non-neoplastic disease, or with pleural plaques, were excluded. 21 had SMRP above 1 nM and 38 at or below 1 nM. Study dates were not given.
• Exposure: Past occupational asbestos exposure, recorded by questionnaire on duration and job task. The article did not report which fiber types or doses the participants had. The genetic variants studied were rs1057147 (G to A) and rs57272256 (C to T) in the 3' untranslated region of the mesothelin gene (MSLN).
• Main results:
  • Among the 59 subjects, 18 carried the A variant of rs1057147 (18 GA, 0 AA). 8 carried the T variant of rs57272256 (7 CT, 1 TT).
  • Mean SMRP was 0.80 nM in the GG group for rs1057147 and 1.11 nM in A-variant carriers. The difference was statistically significant (p = 0.016).
  • For rs57272256, mean SMRP was 0.86 nM in the CC group and 1.10 nM in T-variant carriers. The difference was not statistically significant (p = 0.18).
  • GA carriers of rs1057147 made up 11 of the 21 subjects (52.4%) with SMRP above 1.0 nM, and 7 of the 38 subjects (18.4%) with SMRP at or below 1.0 nM (table 3, p = 0.008). For rs57272256, CT or TT carriers made up 5 of 21 (23.8%) above 1.0 nM and 3 of 38 (7.9%) at or below (p = 0.097).
  • Computer-based prediction indicated that rs1057147 was the only region in the 3' untranslated region offering microRNA binding sites. A total of 18 microRNAs might bind there.
• The authors' conclusion: The authors concluded that genetic variation may account, at least in part, for increased SMRP levels in healthy subjects. They stated that further studies are warranted.
• Limitations the authors state:
  • The study was based on a relatively small number of subjects.
  • The rs57272256 variant was infrequent. With only eight carriers, the study lacked adequate statistical power for that variant.
  • The authors said it is difficult to explain a causal relationship between the variant and serum protein levels.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis.

Medical terms in this study, explained in our Lexicon: Mesothelin, Soluble Mesothelin-Related Peptides (SMRP), Pleural Mesothelioma.

Related studies

• A common polymorphism within MSLN affects miR-611 binding site and soluble mesothelin levels in healthy people — S. Garritano, C. De Santi, et al. (2014)
• Two novel polymorphisms in 5' flanking region of the mesothelin gene are associated with soluble mesothelin-related peptide (SMRP) levels — A. Cristaudo, R. Foddis, et al. (2011)
• Soluble mesothelin-related peptide level elevation in mesothelioma serum and pleural effusions — H.I. Pass, A. Wali, et al. (2008)
• Comparison of osteopontin, megakaryocyte potentiating factor, and mesothelin proteins as markers in the serum of patients with malignant mesothelioma — J. Creaney, D. Yeoman, et al. (2008)
• Mesothelin promoter variants are associated with increased soluble mesothelin-related peptide levels in asbestos-exposed individuals — C. De Santi, P. Pucci, et al. (2017)
• Serum levels of soluble mesothelin-related peptides in malignant and nonmalignant asbestos-related pleural disease: relation with past asbestos exposure — J.A. Rodríguez Portal, E. Rodríguez Becerra, et al. (2009)

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