A novel gene variation of TNFalpha associated with ankylosing spondylitis: a reconfirmed study.
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.


CONCLUSIONS
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.
Zhu
Xiaoquan
X
Chinese Academy of Medical Sciences and Peking Union Medical College, China.
Wang
Yawen
Y
Sun
Liang
L
Song
Yuguo
Y
Sun
Fei
F
Tang
Lei
L
Huo
Zhenghao
Z
Li
Jianxin
J
Yang
Ze
Z
D000293:Adolescent; D000328:Adult; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015796:HLA-B27 Antigen / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D015796:HLA-B27 Antigen; D014409:Tumor Necrosis Factor-alpha