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The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype

Rueda, B.; Broen, J.; Simeon, C.; Hesselstrand, Roger LU ; Diaz, B.; Suarez, H.; Ortego-Centeno, N.; Riemekasten, G.; Fonollosa, V. and Vonk, M. C., et al. (2009) In Human Molecular Genetics 18(11). p.2071-2077
Abstract
The aim of this study was to investigate the possible role of STAT4 gene in the genetic predisposition to systemic sclerosis (SSc) susceptibility or clinical phenotype. A total of 1317 SSc patients [896 with limited cutaneous SSc (lcSSc) and 421 with diffuse cutaneous SSc (dcSSc)] and 3113 healthy controls, from an initial case-control set of Spanish Caucasian ancestry and five independent cohorts of European ancestry (The Netherlands, Germany, Sweden, Italy and USA), were included in the study. The rs7574865 polymorphism was selected as STAT4 genetic marker. We observed that the rs7574865 T allele was significantly associated with susceptibility to lcSSc in the Spanish population [P = 1.9 x 10(-5) odds ratio (OR) 1.61 95% confidence... (More)
The aim of this study was to investigate the possible role of STAT4 gene in the genetic predisposition to systemic sclerosis (SSc) susceptibility or clinical phenotype. A total of 1317 SSc patients [896 with limited cutaneous SSc (lcSSc) and 421 with diffuse cutaneous SSc (dcSSc)] and 3113 healthy controls, from an initial case-control set of Spanish Caucasian ancestry and five independent cohorts of European ancestry (The Netherlands, Germany, Sweden, Italy and USA), were included in the study. The rs7574865 polymorphism was selected as STAT4 genetic marker. We observed that the rs7574865 T allele was significantly associated with susceptibility to lcSSc in the Spanish population [P = 1.9 x 10(-5) odds ratio (OR) 1.61 95% confidence intervals (CI) 1.29-1.99], but not with dcSSc (P = 0.41 OR 0.84 95% CI 0.59-1.21). Additionally, a dosage effect was observed showing individuals with rs7574865 TT genotype higher risk for lcSSc (OR 3.34, P = 1.02 x 10(-7) 95% CI 2.11-5.31). The association of the rs7574865 T allele with lcSSc was confirmed in all the replication cohorts with different effect sizes (OR ranging between 1.15 and 1.86), as well as the lack of association of STAT4 with dcSSc. A meta-analysis to test the overall effect of the rs7574865 polymorphism showed a strong risk effect of the T allele for lcSSc susceptibility (pooled OR 1.54 95% CI 1.36-1.74; P < 0.0001). Our data show a strong and reproducible association of the STAT4 gene with the genetic predisposition to lcSSc suggesting that this gene seems to be one of the genetic markers influencing SSc phenotype. (Less)
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published
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Human Molecular Genetics
volume
18
issue
11
pages
2071 - 2077
publisher
Oxford University Press
external identifiers
  • wos:000265951600016
  • scopus:65549154046
ISSN
0964-6906
DOI
10.1093/hmg/ddp119
language
English
LU publication?
yes
id
ce5b142c-0b92-48e1-b882-34dbf828f946 (old id 1426049)
date added to LUP
2009-06-26 13:46:03
date last changed
2017-11-19 03:26:25
@article{ce5b142c-0b92-48e1-b882-34dbf828f946,
  abstract     = {The aim of this study was to investigate the possible role of STAT4 gene in the genetic predisposition to systemic sclerosis (SSc) susceptibility or clinical phenotype. A total of 1317 SSc patients [896 with limited cutaneous SSc (lcSSc) and 421 with diffuse cutaneous SSc (dcSSc)] and 3113 healthy controls, from an initial case-control set of Spanish Caucasian ancestry and five independent cohorts of European ancestry (The Netherlands, Germany, Sweden, Italy and USA), were included in the study. The rs7574865 polymorphism was selected as STAT4 genetic marker. We observed that the rs7574865 T allele was significantly associated with susceptibility to lcSSc in the Spanish population [P = 1.9 x 10(-5) odds ratio (OR) 1.61 95% confidence intervals (CI) 1.29-1.99], but not with dcSSc (P = 0.41 OR 0.84 95% CI 0.59-1.21). Additionally, a dosage effect was observed showing individuals with rs7574865 TT genotype higher risk for lcSSc (OR 3.34, P = 1.02 x 10(-7) 95% CI 2.11-5.31). The association of the rs7574865 T allele with lcSSc was confirmed in all the replication cohorts with different effect sizes (OR ranging between 1.15 and 1.86), as well as the lack of association of STAT4 with dcSSc. A meta-analysis to test the overall effect of the rs7574865 polymorphism showed a strong risk effect of the T allele for lcSSc susceptibility (pooled OR 1.54 95% CI 1.36-1.74; P &lt; 0.0001). Our data show a strong and reproducible association of the STAT4 gene with the genetic predisposition to lcSSc suggesting that this gene seems to be one of the genetic markers influencing SSc phenotype.},
  author       = {Rueda, B. and Broen, J. and Simeon, C. and Hesselstrand, Roger and Diaz, B. and Suarez, H. and Ortego-Centeno, N. and Riemekasten, G. and Fonollosa, V. and Vonk, M. C. and van den Hoogen, F. H. J. and Sanchez-Roman, J. and Aguirre-Zamorano, M. A. and Garcia-Portales, R. and Pros, A. and Camps, M. T. and Gonzalez-Gay, M. A. and Coenen, M. J. H. and Airo, P. and Beretta, L. and Scorza, R. and van Laar, J. and Gonzalez-Escribano, M. F. and Nelson, J. L. and Radstake, T. R. D. J. and Martin, J.},
  issn         = {0964-6906},
  language     = {eng},
  number       = {11},
  pages        = {2071--2077},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype},
  url          = {http://dx.doi.org/10.1093/hmg/ddp119},
  volume       = {18},
  year         = {2009},
}