Comprehensive exploration of the effects of miRNA SNPs on monocyte gene expression

Greliche, Nicolas, Zeller, Tanja, Wild, Philipp S., Rotival, Maxime, Schillert, Arne, Ziegler, Andreas, Deloukas, Panos, Erdmann, Jeanette, Hengstenberg, Christian, Ouwehand, Willem H., Samani, Nilesh J., Schunkert, Heribert, Munzel, Thomas, Lackner, Karl J., Cambien, François, Goodall, Alison H., Tiret, Laurence, Blankenberg, Stefan, Trégouët, David-Alexandre, and Cardiogenics Consortium, (2012) Comprehensive exploration of the effects of miRNA SNPs on monocyte gene expression. PLoS ONE, 7 (9). e45863. pp. 1-12.

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Abstract

We aimed to assess whether pri-miRNA SNPs (miSNPs) could influence monocyte gene expression, either through marginal association or by interacting with polymorphisms located in 3'UTR regions (3utrSNPs). We then conducted a genome-wide search for marginal miSNPs effects and pairwise miSNPs × 3utrSNPs interactions in a sample of 1,467 individuals for which genome-wide monocyte expression and genotype data were available. Statistical associations that survived multiple testing correction were tested for replication in an independent sample of 758 individuals with both monocyte gene expression and genotype data. In both studies, the hsa-mir-1279 rs1463335 was found to modulate in cis the expression of LYZ and in trans the expression of CNTN6, CTRC, COPZ2, KRT9, LRRFIP1, NOD1, PCDHA6, ST5 and TRAF3IP2 genes, supporting the role of hsa-mir-1279 as a regulator of several genes in monocytes. In addition, we identified two robust miSNPs × 3utrSNPs interactions, one involving HLA-DPB1 rs1042448 and hsa-mir-219-1 rs107822, the second the H1F0 rs1894644 and hsa-mir-659 rs5750504, modulating the expression of the associated genes. As some of the aforementioned genes have previously been reported to reside at disease-associated loci, our findings provide novel arguments supporting the hypothesis that the genetic variability of miRNAs could also contribute to the susceptibility to human diseases.

Item ID: 41578
Item Type: Article (Research - C1)
ISSN: 1932-6203
Additional Information:

© Greliche et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

The Gutenberg Health Study is funded through the government of Rheinland-Pfalz ("Stiftung Rheinland Pfalz für Innovation", contract AZ 961-386261/733), the research programs "Wissen schafft Zukunft" and "Schwerpunkt Vaskuläre Prävention" of the Johannes Gutenberg-University of Mainz and its contract with Boehringer Ingelheim and PHILIPS Medical Systems including an unrestricted grant for the Gutenberg Health Study.

Funders: National Genome "NGFNplus", Federal Ministry of Education and Research, Germany, Agence Nationale de la Recherche, France, European Union FP6 program
Projects and Grants: National Genome "NGFNplus" contract A3 01GS0833, National Genome "NGFNplus" contract A3 01GS0831, Federal Ministry of Education and Research contract BMBF 01KU0908A, Agence Nationale de la Recherche contract ANR 09 GENO 106 01, European Union FP6 program LSHM-CT-2006-037593
Date Deposited: 09 Dec 2015 23:32
FoR Codes: 01 MATHEMATICAL SCIENCES > 0104 Statistics > 010402 Biostatistics @ 40%
06 BIOLOGICAL SCIENCES > 0604 Genetics > 060412 Quantitative Genetics (incl Disease and Trait Mapping Genetics) @ 60%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 80%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 20%
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