TITLE

TUMOUR NECROSIS FACTOR ALPHA (TNF) GENE HAPLOTYPES AND PRIMARY SCLEROSING CHOLANGITIS

AUTHOR(S)
Cullen, S.N.; Ahmad, T.; Neville, M.; Walton, R.W.; Jewell, D.P.; Chapman, R.W.
PUB. DATE
April 2003
SOURCE
Gut;Apr2003 Supplement 1, Vol. 52, pA107
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Previous studies have demonstrated an association between susceptibility to primary sclerosing cholangitis (PSC) and alleles on the classical autoimmune haplotype including the TNF promoter polymorphism TNF-308A. This study was designed to examine the association of PSC with 5 other polymorphic sites in the TNF promoter region. Methods: 100 patients with accurately characterised PSC, and 357 healthy controls were studied. Genotyping of 6 TNF promoter polymorphisms and high resolution class I and class Il HLA typing was carried out using PCR-SSP. SNPs within the TNF gene were constructed into gene haplotypes using the statistical computer software, PHASE. Analysis was carried out using a Chi-squared test with a Bonferroni correction factor of 7.Results: See Table. Conclusion: PSC is associated with TNF haplotype 2. This contains the variant allele -308A, which has previously been described in association with PSC. This allele is found on the highly conserved autoimmune haplotype A1 B8 DR3. An association between TNF -308A and PSC independent of other alleles on this haplotype was not found. Dissecting out the primary associated allele requires the study of a greater number of informative recombinant haplotypes which can only be achieved by much larger international collaborative studies.
ACCESSION #
9748023

 

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