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A novel gene variation of TNFα associated with ankylosing spondylitis: a reconfirmed study
  1. Xiaoquan Zhu1,2,
  2. Yawen Wang4,6,
  3. Liang Sun3,5,
  4. Yuguo Song4,
  5. Fei Sun3,
  6. Lei Tang3,
  7. Zhenghao Huo7,
  8. Jianxin Li6,
  9. Ze Yang3
  1. 1
    Chinese Academy of Medical Sciences and Peking Union Medical College, China
  2. 2
    National Institute of Geriatrics, Beijing Hospital, Ministry of Health, Beijing, China
  3. 3
    National Institute of Geriatrics, Beijing Hospital, Ministry of Health, Beijing, China
  4. 4
    Department of Rheumatology of the Affiliated Hospital, Beihua University School of Medicine, Jilin, China
  5. 5
    Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
  6. 6
    The Key Laboratory of Reproductive Health, Liaoning, China
  7. 7
    The Basal Medical School, Ningxia Medical College, Ningxia, China
  1. Ze Yang, National Institute of Geriatrics, Beijing Hospital, Ministry of Health, China. 1 Dahua Road, Dong Dan, Beijing 100730, China; yangze016{at}


Background: A great deal of evidence has shown that non-human leucocyte antigen (HLA)-B27 genes may play crucial roles in the aetiology of ankylosing spondylitis (AS), but there is little evidence of a relationship with tumour necrosis factor (TNF)α gene variation. One functional single-nucleotide polymorphism (SNP), −850 C→T, on the TNFα gene promoter region was identified and confirmed to be significantly associated with AS by our recent study.

Objective: To investigate whether the −850 C→T SNP is a susceptibility locus for AS or is only a marker linked to potential disease gene loci in a Chinese population.

Methods: Ten common SNPs were selected from nine inflammatory genes covering the right and left flanking regions of the TNFα gene, which span a region of about 100 kb on chromosome 6p21.31, and a tag SNP in HCP5 gene was used to examine the linkage between the HLA-B27 and TNFα genes. SNPs were genotyped by PCR restriction-fragment length polymorphism (RFLP), allele-specific PCR and restriction site-generating PCR-RFLP for single-base association and linkage disequilibrium (LD).

Results: The prevalence of TNFα-850 C→T SNP was significantly different between case and control groups. A specific haplotype covering TNFα gene mutant was strongly associated with AS. An LD test showed that a recombination between HLA-B27 and TNFα might have taken place.

Conclusion: The TNFα locus was reconfirmed and showed association with susceptibility to AS. It may be independent of HLA-B27. A range of 58 kb covering TNFα had strong LD to AS.

  • TNFα
  • -850
  • association
  • ankylosing spondylitis

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  • Funding: The study is supported partly by National Scientific Foundation of China (30471926, 30671110) and National Basic Research Program of China (973 Program) (2006CB503901) grants to Z Y.

  • The first two authors contributed equally to this work.

  • Abbreviations:
    ankylosing spondylitis
    human leucocyte antigen
    linkage disequilibrium
    nuclear factor
    restriction site-generating
    single-nucleotide polymorphism
    tumour necrosis factor