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Genetic association of miRNA-146a with systemic lupus erythematosus in Europeans through decreased expression of the gene

Lofgren, S. E.; Frostegard, J.; Truedsson, Lennart LU ; Pons-Estel, B. A.; D'Alfonso, S.; Witte, T.; Lauwerys, B. R.; Endreffy, E.; Kovacs, L. and Vasconcelos, C., et al. (2012) In Genes and Immunity 13(3). p.268-274
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... (More)
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. (Less)
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Contribution to journal
publication status
published
subject
keywords
autoimmunity, inflammation, microRNAs, miR146a, systemic lupus, erythematosus
in
Genes and Immunity
volume
13
issue
3
pages
268 - 274
publisher
Nature Publishing Group
external identifiers
  • wos:000303059900009
  • scopus:84859910035
ISSN
1476-5470
DOI
10.1038/gene.2011.84
language
English
LU publication?
yes
id
84e11d93-4011-4636-ba63-ba43b57a05be (old id 2571091)
date added to LUP
2012-06-01 08:54:43
date last changed
2017-11-12 03:13:13
@article{84e11d93-4011-4636-ba63-ba43b57a05be,
  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.},
  author       = {Lofgren, S. E. and Frostegard, J. and Truedsson, Lennart and Pons-Estel, B. A. and D'Alfonso, S. and Witte, T. and Lauwerys, B. R. and Endreffy, E. and Kovacs, L. and Vasconcelos, C. and Martins da Silva, B. and Kozyrev, S. V. and Alarcon-Riquelme, M. E.},
  issn         = {1476-5470},
  keyword      = {autoimmunity,inflammation,microRNAs,miR146a,systemic lupus,erythematosus},
  language     = {eng},
  number       = {3},
  pages        = {268--274},
  publisher    = {Nature Publishing Group},
  series       = {Genes and Immunity},
  title        = {Genetic association of miRNA-146a with systemic lupus erythematosus in Europeans through decreased expression of the gene},
  url          = {http://dx.doi.org/10.1038/gene.2011.84},
  volume       = {13},
  year         = {2012},
}