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Contribution of IKBKE and IFIH1 gene variants to SLE susceptibility

Wang, C.; Ahlford, A.; Laxman, N.; Nordmark, G.; Eloranta, M-L; Gunnarsson, I.; Svenungsson, E.; Padyukov, L.; Sturfelt, Gunnar LU and Jönsen, Andreas LU , et al. (2013) In Genes and Immunity 14(4). p.217-222
Abstract
The type I interferon system genes IKBKE and IFIH1 are associated with the risk of systemic lupus erythematosus (SLE). To identify the sequence variants that are able to account for the disease association, we resequenced the genes IKBKE and IFIH1. Eighty-six single-nucleotide variants (SNVs) with potentially functional effect or differences in allele frequencies between patients and controls determined by sequencing were further genotyped in 1140 SLE patients and 2060 controls. In addition, 108 imputed sequence variants in IKBKE and IFIH1 were included in the association analysis. Ten IKBKE SNVs and three IFIH1 SNVs were associated with SLE. The SNVs rs1539241 and rs12142086 tagged two independent association signals in IKBKE, and the... (More)
The type I interferon system genes IKBKE and IFIH1 are associated with the risk of systemic lupus erythematosus (SLE). To identify the sequence variants that are able to account for the disease association, we resequenced the genes IKBKE and IFIH1. Eighty-six single-nucleotide variants (SNVs) with potentially functional effect or differences in allele frequencies between patients and controls determined by sequencing were further genotyped in 1140 SLE patients and 2060 controls. In addition, 108 imputed sequence variants in IKBKE and IFIH1 were included in the association analysis. Ten IKBKE SNVs and three IFIH1 SNVs were associated with SLE. The SNVs rs1539241 and rs12142086 tagged two independent association signals in IKBKE, and the haplotype carrying their risk alleles showed an odds ratio of 1.68 (P-value = 1.0 x 10(-5)). The risk allele of rs12142086 affects the binding of splicing factor 1 in vitro and could thus influence its transcriptional regulatory function. Two independent association signals were also detected in IFIH1, which were tagged by a low-frequency SNV rs78456138 and a missense SNV rs3747517. Their joint effect is protective against SLE (odds ratio = 0.56; P-value = 6.6 x 10(-3)). In conclusion, we have identified new SLE-associated sequence variants in IKBKE and IFIH1, and proposed functional hypotheses for the association signals. (Less)
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published
subject
keywords
IKBKE, IFIH1, resequencing, association study, systemic lupus, erythematosus
in
Genes and Immunity
volume
14
issue
4
pages
217 - 222
publisher
Nature Publishing Group
external identifiers
  • wos:000320029300003
  • scopus:84878937710
ISSN
1476-5470
DOI
10.1038/gene.2013.9
language
English
LU publication?
yes
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d95260a2-3389-436b-a3d0-483a9f4ee123 (old id 3927129)
date added to LUP
2013-07-16 15:51:32
date last changed
2019-08-04 03:13:44
@article{d95260a2-3389-436b-a3d0-483a9f4ee123,
  abstract     = {The type I interferon system genes IKBKE and IFIH1 are associated with the risk of systemic lupus erythematosus (SLE). To identify the sequence variants that are able to account for the disease association, we resequenced the genes IKBKE and IFIH1. Eighty-six single-nucleotide variants (SNVs) with potentially functional effect or differences in allele frequencies between patients and controls determined by sequencing were further genotyped in 1140 SLE patients and 2060 controls. In addition, 108 imputed sequence variants in IKBKE and IFIH1 were included in the association analysis. Ten IKBKE SNVs and three IFIH1 SNVs were associated with SLE. The SNVs rs1539241 and rs12142086 tagged two independent association signals in IKBKE, and the haplotype carrying their risk alleles showed an odds ratio of 1.68 (P-value = 1.0 x 10(-5)). The risk allele of rs12142086 affects the binding of splicing factor 1 in vitro and could thus influence its transcriptional regulatory function. Two independent association signals were also detected in IFIH1, which were tagged by a low-frequency SNV rs78456138 and a missense SNV rs3747517. Their joint effect is protective against SLE (odds ratio = 0.56; P-value = 6.6 x 10(-3)). In conclusion, we have identified new SLE-associated sequence variants in IKBKE and IFIH1, and proposed functional hypotheses for the association signals.},
  author       = {Wang, C. and Ahlford, A. and Laxman, N. and Nordmark, G. and Eloranta, M-L and Gunnarsson, I. and Svenungsson, E. and Padyukov, L. and Sturfelt, Gunnar and Jönsen, Andreas and Bengtsson, Anders and Truedsson, Lennart and Rantapaa-Dahlqvist, S. and Sjowall, C. and Sandling, J. K. and Ronnblom, L. and Syvanen, A-C},
  issn         = {1476-5470},
  keyword      = {IKBKE,IFIH1,resequencing,association study,systemic lupus,erythematosus},
  language     = {eng},
  number       = {4},
  pages        = {217--222},
  publisher    = {Nature Publishing Group},
  series       = {Genes and Immunity},
  title        = {Contribution of IKBKE and IFIH1 gene variants to SLE susceptibility},
  url          = {http://dx.doi.org/10.1038/gene.2013.9},
  volume       = {14},
  year         = {2013},
}