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

• Published in: Rheumatology (Oxford, England) Vol. 48; no. 11; pp. 1363 - 1368
• Main Authors: Li, Hua, Zou, Qiang, Xie, Zhunyi, Liu, Yang, Zhong, Bing, Yang, Shu, Zheng, Ping, Yang, Fei, Fang, Yongfei, Wu, YuZhang
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.11.2009
• Subjects: Adult; Arthritis, Rheumatoid - ethnology; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Asian Continental Ancestry Group - genetics; Autoantibodies - blood; Biological and medical sciences; Diseases of the osteoarticular system; Female; Gene Frequency; Genetic polymorphisms; Genotype; Haplotypes; Humans; Inflammatory joint diseases; Linkage Disequilibrium; Male; Medical sciences; Middle Aged; Molecular immunology; Peptides, Cyclic - immunology; Phenotype; Polymorphism, Single Nucleotide; Rheumatoid arthritis; Rheumatoid Factor - blood; Single-nucleotide polymorphism; STAT4; STAT4 Transcription Factor - genetics; Immunopathology; Molecular immunology; Diseases of the osteoarticular system; Rheumatology; Autoimmune disease; Inflammatory joint disease; Single-nucleotide polymorphism; Genetic polymorphisms; Rheumatoid factor; Chronic; Immunology; Rheumatoid arthritis; STAT4; Genetics; Single nucleotide polymorphism; Haplotype
• ISSN: 1462-0324; 1462-0332; 1462-0332
• DOI: 10.1093/rheumatology/kep207

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.