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Immunogenetics in PSC

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Immunogenetics in PSC.

son PT, Norris S.

Centre for Liver Research, The School of Clinical Medical Sciences,

The University of Newcastle, Framlington Place, Newcastle-upon-Tyne,

NE2 4HH, UK. p.t.donaldson@...

Primary sclerosing cholangitis (PSC) does not exhibit simple

Mendelian inheritance attributable to a single gene locus and our

knowledge of the genetics of this complex disease is based entirely

on case-control studies of candidate genes. The prime candidates in

PSC are inherited variation (polymorphism) in the genes that regulate

the immune response, especially the genes of the major

histocompatability complex (MHC). Thus far, five different human

leukocyte antigen (HLA) haplotypes have been associated with PSC:

three with increased risk of disease and two with reduced risk. More

recently studies of non-MHC genes have failed to associate PSC with

several cytokine genes (IL-1 and IL-10), with FAS (TNFRSF6), with

TGFbeta-1, or with CCR-5 but have found genetic links with MMP-3 and

disease progression, whilst the potential role of CTLA-4 gene

polymorphism remains in question.With the completion of the human

genome project, understanding the genetics of complex (non-Mendelian)

disease is a major priority for the research community and the

studies summarized herein may guide these future investigations.

Copyright 2001 Harcourt Publishers Ltd.

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