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• W2066460345 abstract "Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the presence of anti-mitochondrial antibodies and chronic inflammatory destruction of septal and intrahepatic bile ducts. Although there are no obvious associations of PBC with MHC class I or class II genes, there appears to be a significant increased risk of developing disease within families. Clearly, a combination of genetic and environmental factors play a role in disease pathogenesis, although the relative contributions of each are unclear. In this study, we have taken advantage of the well-defined health-care system in Hiroshima prefecture, where PBC is a reportable disease. In the period 1988-1997, 156 new patients with PBC in a total population of 2,873,000 were diagnosed. These patients included 18 subjects that were derived from eight different families in which more than one family member had a history of PBC; this reflects a frequency of 5.1% and further shows that the prevalence of PBC is greatly increased in family members. Of interest, the median age of onset of PBC in second generation patients was much younger (33.4+/-10.8 years) compared to median disease onset in general patients with PBC in Hiroshima (55.6+/-12 years). In fact, it was striking that the onset of disease in family members often occurred within a few years of each other. We also noted that sera of affected members had similar AMA reactive profiles against recombinant PDC-E2, BCKD-E2 and OGDC-E2; the major autoantigens of PBC. Similar HLA types were found within affected members of a pedigree but the data is limited because of absence of similar typing of unaffected members. The increased family history of PBC, and the earlier onset of disease in second generation members, suggests that environmental agents are an important risk factor for the development of disease. We suggest that genomic analysis in familial PBC will be important to identify the mechanisms of genetic susceptibility." @default.
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• W2066460345 date "1999-08-01" @default.
• W2066460345 modified "2023-09-23" @default.
• W2066460345 title "Familial Primary Biliary Cirrhosis in Hiroshima" @default.
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• W2066460345 doi "https://doi.org/10.1006/jaut.1999.0299" @default.
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