The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype

Blanca Rueda; J. Broen; C. Simeon; R. Hesselstrand; B. Diaz; H. Suárez; N. Ortego-Centeno; G. Riemekasten; V. Fonollosa; M. C. Vonk; F. H.J. Van den Hoogen; J. Sanchez-Román; M. A. Aguirre-Zamorano; R. García-Portales; A. Pros; M. T. Camps; M. A. Gonzalez-Gay; M. J.H. Coenen; P. Airo; L. Beretta; R. Scorza; J. Van Laar; M. F. Gonzalez-Escribano; J. I. Nelson; T. R.D.J. Radstake; J. Martin

doi:10.1093/hmg/ddp119

The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype

Blanca Rueda, J. Broen, C. Simeon, R. Hesselstrand, B. Diaz, H. Suárez, N. Ortego-Centeno, G. Riemekasten, V. Fonollosa, M. C. Vonk, F. H.J. Van den Hoogen, J. Sanchez-Román, M. A. Aguirre-Zamorano, R. García-Portales, A. Pros, M. T. Camps, M. A. Gonzalez-Gay, M. J.H. Coenen, P. Airo, L. BerettaR. Scorza, J. Van Laar, M. F. Gonzalez-Escribano, J. I. Nelson, T. R.D.J. Radstake, J. Martin^*

^*Korrespondierende/r Autor/-in für diese Arbeit

Klinik für Rheumatologie und klinische Immunologie

138 Zitate (Scopus)

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 × 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 × 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.

Originalsprache	Englisch
Zeitschrift	Human Molecular Genetics
Jahrgang	18
Ausgabenummer	11
Seiten (von - bis)	2071-2077
Seitenumfang	7
ISSN	0964-6906
DOIs	https://doi.org/10.1093/hmg/ddp119
Publikationsstatus	Veröffentlicht - 2009

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Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)

UN SDGs

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Rueda, B., Broen, J., Simeon, C., Hesselstrand, R., Diaz, B., Suárez, H., Ortego-Centeno, N., Riemekasten, G., Fonollosa, V., Vonk, M. C., Van den Hoogen, F. H. J., Sanchez-Román, J., Aguirre-Zamorano, M. A., García-Portales, R., Pros, A., Camps, M. T., Gonzalez-Gay, M. A., Coenen, M. J. H., Airo, P., ... Martin, J. (2009). The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype. Human Molecular Genetics, 18(11), 2071-2077. https://doi.org/10.1093/hmg/ddp119

@article{25e5cfc702194ef7bd199948c3f8604e,

title = "The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype",

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 × 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 × 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.",

author = "Blanca Rueda and J. Broen and C. Simeon and R. Hesselstrand and B. Diaz and H. Su{\'a}rez and N. Ortego-Centeno and G. Riemekasten and V. Fonollosa and Vonk, {M. C.} and {Van den Hoogen}, {F. H.J.} and J. Sanchez-Rom{\'a}n and Aguirre-Zamorano, {M. A.} and R. Garc{\'i}a-Portales and A. Pros and Camps, {M. T.} and Gonzalez-Gay, {M. A.} and Coenen, {M. J.H.} and P. Airo and L. Beretta and R. Scorza and {Van Laar}, J. and Gonzalez-Escribano, {M. F.} and Nelson, {J. I.} and Radstake, {T. R.D.J.} and J. Martin",

year = "2009",

doi = "10.1093/hmg/ddp119",

language = "English",

volume = "18",

pages = "2071--2077",

journal = "Human Molecular Genetics",

issn = "0964-6906",

number = "11",

}

Rueda, B, Broen, J, Simeon, C, Hesselstrand, R, Diaz, B, Suárez, H, Ortego-Centeno, N, Riemekasten, G, Fonollosa, V, Vonk, MC, Van den Hoogen, FHJ, Sanchez-Román, J, Aguirre-Zamorano, MA, García-Portales, R, Pros, A, Camps, MT, Gonzalez-Gay, MA, Coenen, MJH, Airo, P, Beretta, L, Scorza, R, Van Laar, J, Gonzalez-Escribano, MF, Nelson, JI, Radstake, TRDJ & Martin, J 2009, 'The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype', Human Molecular Genetics, Jg. 18, Nr. 11, S. 2071-2077. https://doi.org/10.1093/hmg/ddp119

TY - JOUR

T1 - The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype

AU - Rueda, Blanca

AU - Broen, J.

AU - Simeon, C.

AU - Hesselstrand, R.

AU - Diaz, B.

AU - Suárez, H.

AU - Ortego-Centeno, N.

AU - Riemekasten, G.

AU - Fonollosa, V.

AU - Vonk, M. C.

AU - Van den Hoogen, F. H.J.

AU - Sanchez-Román, J.

AU - Aguirre-Zamorano, M. A.

AU - García-Portales, R.

AU - Pros, A.

AU - Camps, M. T.

AU - Gonzalez-Gay, M. A.

AU - Coenen, M. J.H.

AU - Airo, P.

AU - Beretta, L.

AU - Scorza, R.

AU - Van Laar, J.

AU - Gonzalez-Escribano, M. F.

AU - Nelson, J. I.

AU - Radstake, T. R.D.J.

AU - Martin, J.

PY - 2009

Y1 - 2009

N2 - 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 × 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 × 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.

AB - 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 × 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 × 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.

UR - http://www.scopus.com/inward/record.url?scp=65549154046&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddp119

DO - 10.1093/hmg/ddp119

M3 - Journal articles

C2 - 19286670

AN - SCOPUS:65549154046

SN - 0964-6906

VL - 18

SP - 2071

EP - 2077

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 11

ER -

The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype

Abstract

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