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)alpha gene variation. One functional single-nucleotide polymorphism (SNP), -850 C-->T, on the TNFalpha 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 TNFalpha 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 TNFalpha 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 TNFalpha-850 C-->T SNP was significantly different between case and control groups. A specific haplotype covering TNFalpha gene mutant was strongly associated with AS. An LD test showed that a recombination between HLA-B27 and TNFalpha might have taken place. CONCLUSION: The TNFalpha locus was reconfirmed and showed association with susceptibility to AS. It may be independent of HLA-B27. A range of 58 kb covering TNFalpha had strong LD to AS.
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)alpha gene variation. One functional single-nucleotide polymorphism (SNP), -850 C-->T, on the TNFalpha 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 TNFalpha 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 TNFalpha 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 TNFalpha-850 C-->T SNP was significantly different between case and control groups. A specific haplotype covering TNFalpha gene mutant was strongly associated with AS. An LD test showed that a recombination between HLA-B27 and TNFalpha might have taken place. CONCLUSION: The TNFalpha locus was reconfirmed and showed association with susceptibility to AS. It may be independent of HLA-B27. A range of 58 kb covering TNFalpha had strong LD to AS.
Authors: J Braun; T Pham; J Sieper; J Davis; Sj van der Linden; M Dougados; D van der Heijde Journal: Ann Rheum Dis Date: 2003-09 Impact factor: 19.103
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Authors: John C Davis; Désirée Van Der Heijde; Jurgen Braun; Maxime Dougados; John Cush; Daniel O Clegg; Alan Kivitz; Roy Fleischmann; Robert Inman; Wayne Tsuji Journal: Arthritis Rheum Date: 2003-11
Authors: Won-Tae Chung; Jung-Yoon Choe; Won Cheoul Jang; Su Min Park; Young Chang Ahn; Il Kyu Yoon; Tae-Hwan Kim; Youn-Hyoung Nam; Sung-Hoon Park; Sung-Won Lee; Seong-Kyu Kim Journal: Rheumatol Int Date: 2010-03-28 Impact factor: 2.631