Abstract
Background/Aims: Primary sclerosing cholangitis is associated with the HLA haplotypes A1-B8-DRB3*0101-DRB1*0301-DQA1*0501-DQB1*0201 and DRB3*0101-DRB1*1301-DQA1*0103-DQB1*0603. However, the interpretation of these genetic associations is controversial. One
explanation may be that HLA-encoded susceptibility is due to other genes carried on
these haplotypes such as the HLA class III tumor necrosis factor genes. The aim of
the study was to investigate tumor necrosis factor genetics in a large series of well-defined
patients.
Methods: One hundred and ten HLA genotyped patients and 126 control subjects were studied
by polymerase chain reaction genotyping for 3 different tumor necrosis factor gene
polymorphisms: −308, −238 and an Nco1 restriction fragment length polymorphism in the lymphotoxin α gene.
Results: Overall, 58% of patients had the TNF2 allele, compared with 29% of controls, pc=0.0001. No association was found with either of the other tumor necrosis factor polymorphisms
examined. TNF2 was significantly increased in the presence of B8 and DRB3*0101 only, and was independent of DRB1*0301 (pc<0.04). The associations with B8 and TNF2 were stronger than the associations with any of the HLA class II alleles examined.
Conclusion: HLA-encoded genetic susceptibility to primary sclerosing cholangitis may be determined
by polymorphism within the HLA class III region, in particular with the TNF2 allele.
Keywords
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Article info
Publication history
Accepted:
July 14,
1998
Received in revised form:
July 6,
1998
Received:
April 15,
1998
Identification
Copyright
© 1999 Published by Elsevier Inc.
