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-α gene variation. One functional single nucleotide polymorphism (SNP), -850 C→T on the TNF-α 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 C→T 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-α 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-α. 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-α-850 CNT SNP was significantly different between case-control groups. A specific haplotype covering TNF-αgene mutant was strongly associated with AS. LD test showed that the recombination between HLA-B27 and TNF-α might be taken place.
Conclusion: The TNF-α locus was reconfirmed and showed association with susceptibility to AS and could be independent of HLA-B27. A range of 58kb covering TNF-α was strong LD to AS.
- ankylosing spondylitis