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A STAT4 risk allele is associated with ischaemic cerebrovascular events and anti-phospholipid antibodies in systemic lupus erythematosus

Svenungsson, Elisabet; Gustafsson, Johanna; Leonard, Dag; Sandling, Johanna; Gunnarsson, Iva; Nordmark, Gunnel; Jönsen, Andreas LU ; Bengtsson, Anders LU ; Sturfelt, Gunnar LU and Rantapaa-Dahlqvist, Solbritt, et al. (2010) In Annals of the Rheumatic Diseases 69(5). p.834-840
Abstract
Objective To investigate whether the risk allele for systemic lupus erythematosus (SLE) in the signal transducer and activator of transcription factor 4 (STAT4) gene, defined by the single nucleotide polymorphism (SNP) rs10181656(G), is associated with vascular events and/or presence of prothrombotic anti-phospholipid antibodies (aPL) in patients with SLE. Methods Two independent groups of unrelated patients with SLE of Swedish ethnicity (n=424 and 154) were genotyped, and occurrence of previous manifestations of ischaemic heart disease (IHD), ischaemic cerebrovascular disease (ICVD) and venous thromboembolic events (VTE) was tabulated. aPL values were measured by ELISA. Matched controls (n=492 and 194) were genotyped. Results The STAT4... (More)
Objective To investigate whether the risk allele for systemic lupus erythematosus (SLE) in the signal transducer and activator of transcription factor 4 (STAT4) gene, defined by the single nucleotide polymorphism (SNP) rs10181656(G), is associated with vascular events and/or presence of prothrombotic anti-phospholipid antibodies (aPL) in patients with SLE. Methods Two independent groups of unrelated patients with SLE of Swedish ethnicity (n=424 and 154) were genotyped, and occurrence of previous manifestations of ischaemic heart disease (IHD), ischaemic cerebrovascular disease (ICVD) and venous thromboembolic events (VTE) was tabulated. aPL values were measured by ELISA. Matched controls (n=492 and 194) were genotyped. Results The STAT4 risk allele was more frequent in patients with SLE with previous arterial events (combined OR (ORc)= 1.5, 95% CI 1.1 to 2.0) compared to patients without such events. The association was mainly attributable to an accumulation of the risk allele among patients with ICVD (OR c = 2.3, CI 1.6 to 3.3). There was no association with IHD or VTE. The presence of two or more aPLs was associated with the risk allele (OR c = 1.6, 95% CI 1.2 to 2.0). In multivariable-adjusted logistic regression analyses treatment for hypertension, at least one STAT4 risk allele, older age, IgG anti-cardiolipin antibodies and longer SLE duration remained independently associated with previous ICVD (p <= 0.02 for all). Conclusion Patients with SLE with the STAT4 risk allele had a strikingly increased risk of ICVD, comparable in magnitude to that of hypertension. The results imply that a genetic predisposition is an important and previously unrecognised risk factor for ICVD in SLE, and that aPLs may be one underlying mechanism. (Less)
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published
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Annals of the Rheumatic Diseases
volume
69
issue
5
pages
834 - 840
publisher
British Medical Association
external identifiers
  • wos:000276982300011
  • scopus:77951563846
ISSN
1468-2060
DOI
10.1136/ard.2009.115535
language
English
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yes
id
300cdbcb-9f34-446f-ade7-e670da63cdcb (old id 1601902)
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2010-05-20 08:49:30
date last changed
2018-05-29 09:48:30
@article{300cdbcb-9f34-446f-ade7-e670da63cdcb,
  abstract     = {Objective To investigate whether the risk allele for systemic lupus erythematosus (SLE) in the signal transducer and activator of transcription factor 4 (STAT4) gene, defined by the single nucleotide polymorphism (SNP) rs10181656(G), is associated with vascular events and/or presence of prothrombotic anti-phospholipid antibodies (aPL) in patients with SLE. Methods Two independent groups of unrelated patients with SLE of Swedish ethnicity (n=424 and 154) were genotyped, and occurrence of previous manifestations of ischaemic heart disease (IHD), ischaemic cerebrovascular disease (ICVD) and venous thromboembolic events (VTE) was tabulated. aPL values were measured by ELISA. Matched controls (n=492 and 194) were genotyped. Results The STAT4 risk allele was more frequent in patients with SLE with previous arterial events (combined OR (ORc)= 1.5, 95% CI 1.1 to 2.0) compared to patients without such events. The association was mainly attributable to an accumulation of the risk allele among patients with ICVD (OR c = 2.3, CI 1.6 to 3.3). There was no association with IHD or VTE. The presence of two or more aPLs was associated with the risk allele (OR c = 1.6, 95% CI 1.2 to 2.0). In multivariable-adjusted logistic regression analyses treatment for hypertension, at least one STAT4 risk allele, older age, IgG anti-cardiolipin antibodies and longer SLE duration remained independently associated with previous ICVD (p &lt;= 0.02 for all). Conclusion Patients with SLE with the STAT4 risk allele had a strikingly increased risk of ICVD, comparable in magnitude to that of hypertension. The results imply that a genetic predisposition is an important and previously unrecognised risk factor for ICVD in SLE, and that aPLs may be one underlying mechanism.},
  author       = {Svenungsson, Elisabet and Gustafsson, Johanna and Leonard, Dag and Sandling, Johanna and Gunnarsson, Iva and Nordmark, Gunnel and Jönsen, Andreas and Bengtsson, Anders and Sturfelt, Gunnar and Rantapaa-Dahlqvist, Solbritt and Elvin, Kerstin and Sundin, Ulf and Garnier, Sophie and Simard, Julia F. and Sigurdsson, Snaevar and Padyukov, Leonid and Syvanen, Ann-Christine and Ronnblom, Lars},
  issn         = {1468-2060},
  language     = {eng},
  number       = {5},
  pages        = {834--840},
  publisher    = {British Medical Association},
  series       = {Annals of the Rheumatic Diseases},
  title        = {A STAT4 risk allele is associated with ischaemic cerebrovascular events and anti-phospholipid antibodies in systemic lupus erythematosus},
  url          = {http://dx.doi.org/10.1136/ard.2009.115535},
  volume       = {69},
  year         = {2010},
}