Association of STAT4 with rheumatoid arthritis: A replication study in three European populations

• Published in: Arthritis and rheumatism Vol. 58; no. 7; pp. 1974 - 1980
• Main Authors: Orozco, Gisela, Alizadeh, Behrooz Z., Delgado‐Vega, Angélica M., González‐Gay, Miguel Á., Balsa, Alejandro, Pascual‐Salcedo, Dora, Fernández‐Gutierrez, Benjamín, González‐Escribano, María F., Petersson, Ingemar F., van Riel, Piet L. C. M., Barrera, Pilar, Coenen, Marieke J. H., Radstake, Timothy R. D. J., van Leeuwen, Miek A., Wijmenga, Cisca, Koeleman, Bobby P. C., Alarcón‐Riquelme, Marta, Martín, Javier
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2008; Wiley
• Subjects: Arthritis, Rheumatoid - genetics; Biological and medical sciences; Case-Control Studies; Clinical Medicine; Diseases of the osteoarticular system; Female; Humans; Inflammatory joint diseases; Klinisk medicin; Male; Medical and Health Sciences; Medical sciences; MEDICIN; Medicin och hälsovetenskap; MEDICINE; Netherlands; Polymorphism, Single Nucleotide; Reumatologi och inflammation; Rheumatology and Autoimmunity; Spain; STAT4 Transcription Factor - genetics; Sweden; Netherlands; Sweden; Spain; Immunopathology; Chronic; Rheumatoid arthritis; Diseases of the osteoarticular system; Rheumatology; Autoimmune disease; Replication; Inflammatory joint disease
• ISSN: 0004-3591; 1529-0131; 1529-0131
• DOI: 10.1002/art.23549

Objective This study was undertaken to investigate the previously reported association of the STAT4 polymorphism rs7574865 with rheumatoid arthritis (RA) in 3 different European populations from Spain, Sweden, and The Netherlands, comprising a total of 2,072 patients and 2,474 controls. Methods Three different cohorts were included in the study: 923 RA patients and 1,296 healthy controls from Spain, 273 RA patients and 285 healthy controls from Sweden, and 876 RA patients and 893 healthy controls from The Netherlands. DNA from patients and controls was obtained from peripheral blood. Samples were genotyped for the STAT4 single‐nucleotide polymorphism rs7574865 using a TaqMan 5′‐allele discrimination assay. The chi‐square test was performed to compare allele and genotype distributions. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results We observed a significantly increased frequency of the minor T allele in RA patients compared with healthy controls in the Spanish population (24.8% versus 20.8%; P = 0.001, OR 1.26 [95% CI 1.09–1.45]). This association was confirmed in both the Swedish population (P = 0.03, OR 1.35 [95% CI 1.03–1.77]) and the Dutch population (P = 0.03, OR 1.45 [95% CI 1.21–1.73]). The overall P value for all 3 populations was 9.79 × 10−6 (OR 1.25 [95% CI 1.13–1.37]). No association between rs7574865 and the presence of rheumatoid factor or anti–cyclic citrullinated peptide autoantibodies was observed. A meta‐analysis of all published STAT4 associations revealed an OR of 1.25 (95% CI 1.19–1.33) (P = 1 × 10−5). Conclusion Our findings indicate an association between the STAT4 polymorphism rs7574865 and RA in 3 different populations, from Spain, Sweden, and The Netherlands, thereby confirming previous data.