Rheumatology Advance Access originally published online on September 8, 2009
Rheumatology 2009 48(11):1363-1368; doi:10.1093/rheumatology/kep207
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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
1Institute of Immunology of PLA, College of Basic Medical Sciences in the Third Military Medical University, Chongqing, 2Department of Immunology, Chengdu Medical College, Chengdu, 3Department of Rheumatology, Southwest Hospital, Chongqing and 4Department of Public Health, Chengdu Medical College, Chengdu, China.
Correspondence to: Yuzhang Wu, Institute of Immunology of PLA, College of Basic Medical Sciences in the Third Military Medical University, Chongqing, 400038, PR China, E-mail: wuyuzhang{at}yahoo.com
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Abstract |
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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).
Conclusion. 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.
KEY WORDS: Rheumatoid arthritis, Genetic polymorphisms, Single-nucleotide polymorphism, Molecular immunology, STAT4
*Hua Li and Qiang Zou equally contributed to this work.
Submitted 25 March 2009;
revised version accepted 17 June 2009.
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