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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

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Genetic variants in miR-146a, miR-149, miR-196a2, miR-499 and their influence on relative expression in lung cancers

Serena Vinci1 / Stefania Gelmini1 / Nicola Pratesi1 / Simona Conti1 / Francesca Malentacchi1 / Lisa Simi1 / Mario Pazzagli1 / 1

1Clinical Biochemistry, Department of Clinical Physiopathology, University of Florence, Florence, Italy

Corresponding author: Claudio Orlando, Clinical Biochemistry, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy Phone: +39 55 4271440, Fax: +39 55 4271371

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM). Volume 49, Issue 12, Pages 2073–2080, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: 10.1515/CCLM.2011.708, September 2011

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Background: The presence of sequence variants in miRNA genes may influence their processing, expression and binding to target mRNAs. Since single miRNA can have a large number of potential mRNA targets, even minor variations in its expression can have influences on hundreds of putative mRNAs.

Methods: Here, we evaluated 101 paired samples (cancer and normal tissues) from non-small cell lung carcinoma (NSCLC) patients to study the genotype distribution of single nucleotide polymorphisms (SNPs) in miR-146a (rs2910164 C-G), miR-149 (rs2292832 C-T), miR-196a2 (rs11614913 C-T) and miR-499 (rs3746444 G-A) and their influence on the expression of respective miRNAs.

Results: Relative expression of miR-146a, miR-149 and miR-499 were comparable in NSCLC and in paired control tissues. On the contrary, we clearly detected a significant increase (p<0.001) of miR-196a2 expression in NSCLC. In particular we found a significant association between miR-196a2 CC genotype and high expression, whereas TT geno-type showed a very low expression in comparison to both CT (p<0.005) and CC patients (p<0.01). We did not find any association between miR-149, miR-196a2 and miR-499 genotype and risk of NSCLC. Conversely, CG genotype of miR-146a appeared associated to an increased risk for NSCLC (p=0.042 and 1.77 OR).

Conclusions: Our results seem to demonstrate that sequence variants of miR-196a2 can have an influence on its expression, while miR-146a can have a role in increasing the risk of NSCLC.

Keywords: high resolution melting analysis; miRNA expression; miRNA genotypes

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