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DEFINING THE IMMUNOGENETIC SUSCEPTIBILITY TO PRIMARY BILIARY-CIRRHOSIS

MEHAL, WZ; GREGORY, WL; LO, YMD; CROSS, SJ; FLEMING, KA; BASSENDINE, MF; JAMES, OFW; (1994) DEFINING THE IMMUNOGENETIC SUSCEPTIBILITY TO PRIMARY BILIARY-CIRRHOSIS. HEPATOLOGY , 20 (5) 1213 - 1219.

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Abstract

Primary biliary cirrhosis is a chronic cholestatic disease, thought to be immune-mediated with genetic susceptibility encoded in the major histocompatibility complex. In northern Europeans, the best established associations are with HLA-DR8 and the complement allele, C4B2. These associations could be due to a single susceptibility locus on an extended haplotype linking HLA-DR8 and C4B2 or to both HLA-DR8 and C4B2 in dependently conferring disease susceptibility. C4B2 genotyping was performed on 64 patients with primary biliary cirrhosis and 61 controls matched for ethnic background and frequency of HLA-DR8. C4B2 was associated with HLA-DR8 (p < 0.05) in PBC. No difference in the frequency of C4B2 was detected between control and disease populations, suggesting that HLA-DR8 and C4B2 are in linkage disequilibrium and that C4B2 is not a susceptibility locus for PBC. Taq I polymorphisms were screened in the disease and control populations with the cosmid probe G91, located midway between the HLA-DR and complement loci. One G91 restriction fragment (G91A) was found to be associated with both HLA-DR8 and C4B2, at equal frequency in health and disease, providing evidence of an HLA-DR8-G91A-C4B2 extended haplotype. The frequency of G91A was the same in the disease and control populations, suggesting that G91A does not confer disease susceptibility. These findings establish G91 as the telomeric boundary for disease susceptibility associated with HLA-DR8, encoded on chromosome six. These studies help define the immunogenetic susceptibility locus for primary biliary cirrhosis.

Type: Article
Title: DEFINING THE IMMUNOGENETIC SUSCEPTIBILITY TO PRIMARY BILIARY-CIRRHOSIS
Keywords: MAJOR HISTOCOMPATIBILITY COMPLEX, ANTIGENS
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)
URI: http://discovery.ucl.ac.uk/id/eprint/1315229
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