Association of STAT4 with rheumatoid arthritis: a replication study in three European populations.
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 x 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 x 10(-5)).


CONCLUSIONS
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.
Orozco
Gisela
G
Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain. gisela@ipb.csic.es
Alizadeh
Behrooz Z
BZ
Delgado-Vega
Angélica M
AM
González-Gay
Miguel A
MA
Balsa
Alejandro
A
Pascual-Salcedo
Dora
D
Fernández-Gutierrez
Benjamín
B
González-Escribano
María F
MF
Petersson
Ingemar F
IF
van Riel
Piet L C M
PL
Barrera
Pilar
P
Coenen
Marieke J H
MJ
Radstake
Timothy R D J
TR
van Leeuwen
Miek A
MA
Wijmenga
Cisca
C
Koeleman
Bobby P C
BP
Alarcón-Riquelme
Marta
M
Martín
Javier
J
D001172:Arthritis, Rheumatoid / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide; D050797:STAT4 Transcription Factor / Q000235:genetics*; D013030:Spain; D013548:Sweden
D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human