A novel gene variation of TNF-alpha associated with ankylosing spondylitis: a reconfirmed study

Xiaoquan Zhu ¹, Yawen Wang ², Liang Sun ³, Yuguo Song ⁴, Fei Sun ⁵, Lei Tang ⁵, Zhenghao Huo ⁶, Jianxin Li ⁷ and Ze Yang ^5*

¹ Chinese Academy of Medical Sciences and Peking Union Medical College, China
² Affiliated Hospital, Beihua University School of Medicine; The Key, China
³ Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, China
⁴ Affiliated Hospital, Beihua University School of Medicine, China
⁵ National Institute of Geriatrics, Beijing Hospital, Ministry of Health, China
⁶ The Basal Medical School, Ningxia Medical College, Ningxia, China
⁷ The Key Laboratory of Reproductive Healthy, Liaoning, China

^* To whom correspondence should be addressed. E-mail: yangze016{at}yahoo.com.cn.

Accepted 14 April 2007

Abstract

Background: Large evidences demonstrated that non-HLA-B27 genes may play crucial roles in etiology of Ankylosing Spondylitis (AS), but it was nearly little related to TNF- gene variation. One functional single nucleotide polymorphism (SNP), -850 CT on the TNF- gene promoter region has been identified and confirmed as significant associated with AS by our studies recently.

Objective: To reconfirm and determine our hypothesis whether -850 CT SNP is a susceptible locus to AS or is only a marker linked to potential disease gene loci in Chinese population.

Methods: Ten common SNPs were selected from nine inflammatory genes covering the right and left flanks of TNF- gene, which span about 100kb region on chromosome 6p21.31, and a tag SNP in HCP5 gene was used to examine the linkage between HLA-B27 and TNF-. SNPs were genotyped by PCR-RFLP, AS-PCR and RG-PCR-RFLP for single-based association and linkage disequilibrium (LD) test.

Results: The prevalence of TNF--850 C��NT SNP was significantly different between case-control groups. A specific haplotype covering TNF-gene mutant was strongly associated with AS. LD test showed that the recombination between HLA-B27 and TNF- might be taken place.

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

Keywords: -850, TNF-alpha, ankylosing spondylitis, association

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This article has been cited by other articles:

• Brown, M A (2008). Zhu et al, "A novel gene variation of TNF{alpha} associated with ankylosing spondylitis: a reconfirmed study". Ann Rheum Dis 67: 434-434 [Full Text]  
• Zhu, X, Yang, Z (2008). TNF{alpha} gene variants and ankylosing spondylitis. Ann Rheum Dis 67: 434-436 [Full Text]