Objectives Recent association studies by the Australo-Anglo-American Spondyloarthritis Consortium (TASC) in Caucasian European populations from Australia, North America and the UK have identified a number of genes as being associated with ankylosing spondylitis (AS). A candidate gene study in a Han Chinese population was performed based on these findings to identify associated genes in this population.
Methods A case-control study was performed in a Han Chinese population of patients with AS (n=775) and controls (n=1587) from Shanghai and Nanjing. All patients met the modified New York criteria for AS. The cases and controls were genotyped for 115 single nucleotide polymorphisms (SNPs) tagging IL23R, ERAP1, STAT3, JAK2, TNFRSF1A and TRADD, as well as other confirmation SNPs from the TASC study, using the Sequenom iPlex and the ABI OpenArray platforms. Statistical analysis of genotyped SNPs was performed using the Cochran–Armitage test for trend and meta-analysis was performed using METAL. SNPs in AS-associated genes in this study were then imputed using MaCH, and association with AS tested by logistic regression.
Results SNPs in TNFRSF1A (rs4149577, p=8.2×10−4), STAT3 (rs2293152, p=0.0015; rs1053005, p=0.017) and ERAP1 (rs27038, p=0.0091; rs27037, p=0.0092) were significantly associated with AS in Han Chinese. Association was also observed between AS and the intergenic region 2p15 (rs10865331, p=0.023). The lack of association between AS and IL23R in Han Chinese was confirmed (all SNPs p>0.1).
Conclusions The study results demonstrate for the first time that genetic polymorphisms in STAT3, TNFRSF1A and 2p15 are associated with AS in Han Chinese, suggesting common pathogenic mechanisms for the disease in Chinese and Caucasian European populations. Furthermore, previous findings demonstrating that ERAP1, but not IL23R, is associated with AS in Chinese patients were confirmed.
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MAB and HX are equal senior authors.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the Shanghai Changzheng Hospital, The Second Military Medical University Hospital, Shanghai 200003, China.
Provenance and peer review Not commissioned; externally peer reviewed.
The Australo-Anglo-American Spondyloarthritis Consortium (TASC) are: John D Reveille, Rheumatology and Clinical Immunogenetics, University of Texas Health Science Center at Houston, Houston, Texas, USA; David M Evans, MRC Centre for Causal Analyses in Translational Epidemiology, Department of Social Medicine, University of Bristol, Bristol, UK; Laurie Savage, The Spondylitis Association of America, Sherman, Oaks, California, USA; Michael M Ward, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland, USA; Michael H Weisman, Department of Medicine/Rheumatology, Cedars-Sinai Medical Centre, Los Angeles, California, USA; B Paul Wordsworth, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, UK; Matthew A Brown, The University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia.