Shared genetic risk factors in autoimmune liver disease

To determine if shared genetic risk factors for autoimmune liver disease af fect clinical manifestations, we evaluated 271 patients and 92 normal subje cts by DNA-based techniques. Genetic risk factors were intermixed in all co nditions, and frequency varied according to disease type. DR4 distinguished autoimmune hepatitis (P = 0.0002) and primary biliary cirrhosis (P = 0.004 ) from primary sclerosing cholangitis. DR52 distinguished primary sclerosin g cholangitis from autoimmune hepatitis (P = 0.0007) and primary biliary ci rrhosis (P = 0.00007) and DR3 distinguished autoimmune hepatitis (P = 0.002 ) and primary sclerosing cholangitis (P = 0.0005) from primary biliary cirr hosis. Only the occurrence of DR4 in primary sclerosing cholangitis was low er than in normal subjects (P = 0.02). Patients with mixed genetic risk fac tors did not have distinctive features or manifestations of hybrid conditio ns. We conclude that patients with shared genetic risk factors do not have characteristic features nor do they have overlap syndromes. DR4 may be prot ective against primary sclerosing cholangitis.