Genetic association of miRNA-146a with systemic lupus erythematosus in Europeans through decreased expression of the gene
Open Access
- 5 January 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Genes & Immunity
- Vol. 13 (3), 268-274
- https://doi.org/10.1038/gene.2011.84
Abstract
A recent genome-wide association study revealed a variant (rs2431697) in an intergenic region, between the pituitary tumor-transforming 1 (PTTG1) and microRNA (miR-146a) genes, associated with systemic lupus erythematosus (SLE) susceptibility. Here, we analyzed with a case–control design this variant and other candidate polymorphisms in this region together with expression analysis in order to clarify to which gene this association is related. The single-nucleotide polymorphisms (SNPs) rs2431697, rs2910164 and rs2277920 were genotyped by TaqMan assays in 1324 SLE patients and 1453 healthy controls of European ancestry. Genetic association was statistically analyzed using Unphased. Gene expression of PTTG1, the miRNAs miR-3142 and primary and mature forms of miR-146a in peripheral blood mononuclear cells (PBMCs) were assessed by quantitative real-time PCR. Of the three variants analyzed, only rs2431697 was genetically associated with SLE in Europeans. Gene expression analysis revealed that this SNP was not associated with PTTG1 expression levels, but with the microRNA-146a, where the risk allele correlates with lower expression of the miRNA. We replicated the genetic association of rs2341697 with SLE in a case–control study in Europeans and demonstrated that the risk allele of this SNP correlates with a downregulation of the miRNA 146a, potentially important in SLE etiology.This publication has 36 references indexed in Scilit:
- The rs2910164:G>C SNP in the MIR146A gene is not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriersHuman Mutation, 2011
- MicroRNAs in rheumatoid arthritisFEBS Letters, 2011
- Association analyses identify six new psoriasis susceptibility loci in the Chinese populationNature Genetics, 2010
- miRNAs in human cancerThe Journal of Pathology, 2010
- Function of miR-146a in Controlling Treg Cell-Mediated Regulation of Th1 ResponsesCell, 2010
- microRNAs and the immune responseCurrent Opinion in Pharmacology, 2009
- MicroRNA in autoimmunity and autoimmune diseasesJournal of Autoimmunity, 2009
- Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinomaProceedings of the National Academy of Sciences of the United States of America, 2008
- Expression of microRNA‐146 in rheumatoid arthritis synovial tissueArthritis & Rheumatism, 2008
- NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responsesProceedings of the National Academy of Sciences of the United States of America, 2006