A haplotype in STAT4 gene associated with rheumatoid arthritis in Caucasians is not associated in the Han Chinese population, but with the presence of rheumatoid factor.
OBJECTIVE
Several studies have shown that a haplotype (rs11889341, rs7574865, rs8179673 and rs10181656) in STAT4 is associated with the development of RA in Caucasian, Korean and Japanese populations. The aim of this study was to investigate the effect of STAT4 on susceptibility to RA in the Han Chinese population.


METHODS
Unrelated 750 RA patients and individually matched 750 healthy controls were genotyped for single nucleotide polymorphism (SNP), rs11889341, in STAT4, which tags the susceptibility haplotype. Association analyses were performed on the whole data set and on sex subsets. Significant relationships were determined between clinical variables and rs11889341 for each disease subtype in the studied groups.


RESULTS
There was no evidence of a significant association between rs11889341 and RA. The heterozygous CT genotype was associated with RA in female group [P = 0.027; odds ratio (OR) 1.31; 95% CI 1.03, 1.65]. No association was found in male group and in any subsets of RA based on sex, RF and anti-cyclic citrullinated peptide (anti-CCP) antibody. However, in the Han Chinese population with RA disease, we observed a significantly decreased frequency of the minor T allele and TT genotype in the RF-positive subgroup compared with RF-negative subgroup (T allele: P = 0.024; OR 0.73; 95% CI 0.56, 0.95; TT genotype P = 0.013; OR 0.49; 95% CI 0.28, 0.86).


CONCLUSIONS
The STAT4 RA-susceptibility haplotype identified in other previously reported populations has not been replicated in the Han Chinese population with individually matched case-control study design. It is associated only with the presence of RF in the Han Chinese population with RA disease.
Li
Hua
H
Institute of Immunology of PLA, College of Basic Medical Sciences in the Third Military Medical University, Chongqing, 400038, PR China.
Zou
Qiang
Q
Xie
Zhunyi
Z
Liu
Yang
Y
Zhong
Bing
B
Yang
Shu
S
Zheng
Ping
P
Yang
Fei
F
Fang
Yongfei
Y
Wu
YuZhang
Y
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D044466:Asian People / Q000235:genetics; D001323:Autoantibodies / Q000097:blood; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012217:Rheumatoid Factor / Q000097:blood*; D050797:STAT4 Transcription Factor / Q000235:genetics*
D001323:Autoantibodies; D010456:Peptides, Cyclic; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor