title: Comprehensive exploration of the effects of miRNA SNPs on monocyte gene expression.
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.
authors.affiliation: INSERM UMR_S 937, Pierre and Marie Curie University (UPMC, Paris 6), Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Greliche
authors.forename: Tanja
authors.initials: T
authors.lastname: Zeller
authors.forename: Philipp S
authors.initials: PS
authors.lastname: Wild
authors.forename: Maxime
authors.initials: M
authors.lastname: Rotival
authors.forename: Arne
authors.initials: A
authors.lastname: Schillert
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.forename: Jeanette
authors.initials: J
authors.lastname: Erdmann
authors.forename: Christian
authors.initials: C
authors.lastname: Hengstenberg
authors.forename: Willem H
authors.initials: WH
authors.lastname: Ouwehand
authors.forename: Nilesh J
authors.initials: NJ
authors.lastname: Samani
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
authors.forename: Thomas
authors.initials: T
authors.lastname: Munzel
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Lackner
authors.forename: François
authors.initials: F
authors.lastname: Cambien
authors.forename: Alison H
authors.initials: AH
authors.lastname: Goodall
authors.forename: Laurence
authors.initials: L
authors.lastname: Tiret
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
authors.forename: David-Alexandre
authors.initials: DA
authors.lastname: Trégouët
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D055106:Genome-Wide Association Study; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016014:Linear Models; D015810:Linkage Disequilibrium; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D034622:RNA Interference; D059467:Transcriptome
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs