The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype

被引：136

作者：

Rueda, B. ^{[1
]}

Broen, J. ^{[2
]}

Simeon, C. ^{[20
]}

Hesselstrand, R. ^{[4
]}

Diaz, B. ^{[5
]}

Suarez, H. ^{[5
]}

Ortego-Centeno, N. ^{[6
]}

Riemekasten, G. ^{[7
]}

Fonollosa, V. ^{[20
]}

Vonk, M. C. ^{[2
]}

van den Hoogen, F. H. J. ^{[8
]}

Sanchez-Roman, J. ^{[9
]}

Aguirre-Zamorano, M. A. ^{[10
]}

Garcia-Portales, R. ^{[11
]}

Pros, A. ^{[12
]}

Camps, M. T. ^{[13
]}

Gonzalez-Gay, M. A. ^{[14
]}

Coenen, M. J. H. ^{[3
]}

Airo, P. ^{[15
]}

Beretta, L.

Scorza, R. ^{[16
]}

van Laar, J. ^{[17
]}

Gonzalez-Escribano, M. F. ^{[18
]}

Nelson, J. L. ^{[19
]}

Radstake, T. R. D. J. ^{[2
]}

Martin, J. ^{[1
]}

机构：

[1] CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18100, Spain

[2] Radboud Univ Nijmegen, Med Ctr, Dept Rheumatol, NL-6525 ED Nijmegen, Netherlands

[3] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands

[4] Univ Lund Hosp, Dept Rheumatol, S-22185 Lund, Sweden

[5] Hosp Univ Cent Asturias, Med Interna Serv, Oviedo, Spain

[6] Hosp Clin Univ, Med Interna Serv, Granada, Spain

[7] Charite, Dept Rheumatol & Clin Immunol, Berlin, Germany

[8] Univ Nijmegen Hosp, Dept Rheumatol, Nijmegen, Netherlands

[9] Hosp Virgen Rocio, Med Interna Serv, Seville, Spain

[10] Hosp Reina Sofia, Ser Reumatol, Cordoba, Spain

[11] Hosp Virgen Victoria, Med Interna Serv, Malaga, Spain

[12] Hosp Mar, Serv Reumatol, Barcelona, Spain

[13] Hosp Carlos Haya, Med Interna Serv, Malaga, Spain

[14] Hosp Xeral Calde, Serv Reumatol, Lugo, Spain

[15] Clin Spedali Civili, Serv Reumatol & Immunol, Brescia, Italy

[16] Univ Milan, Referral Ctr Syst Autoimmune Dis, Milan, Italy

[17] Royal Victoria Infirm, Dept Rheumatol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England

[18] Hosp Virgen Rocio, Serv Immunol, Seville, Spain

[19] Univ Washington, Dept Med, Seattle, WA USA

[20] Hosp Valle De Hebron, Med Interna Serv, Barcelona, Spain

来源：

HUMAN MOLECULAR GENETICS | 2009年 / 18卷 / 11期

关键词：

RHEUMATOID-ARTHRITIS; LUPUS-ERYTHEMATOSUS; RISK; ASSOCIATION; SUSCEPTIBILITY; CLASSIFICATION; PATHOGENESIS; CELLS;

D O I：

10.1093/hmg/ddp119

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：2071 / 2077

页数：7

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