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Title: Comprehensive Exploration of the Effects of miRNA SNPs on Monocyte Gene Expression
Authors: Greliche, N.
Zeller, T.
Wild, P. S.
Rotival, M.
Schillert, A.
Ziegler, A.
Deloukas, P.
Erdmann, J.
Hengstenberg, C.
Ouwehand, W. H.
Samani, N. J.
Schunkert, H.
Munzel, T.
Lackner, K. J.
Cambien, F.
Goodall, A. H.
Tiret, L.
Blankenberg, S.
Tregouet, D-A.
First Published: 21-Sep-2012
Publisher: Public Library of Science
Citation: PLoS ONE, 2012, 7 (9), pp. e45863
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.
DOI Link: 10.1371/journal.pone.0045863
ISSN: 1932-6203
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2012 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.
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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