Shared genetic risk factors in autoimmune liver disease.
To determine if shared genetic risk factors for autoimmune liver disease affect clinical manifestations, we evaluated 271 patients and 92 normal subjects by DNA-based techniques. Genetic risk factors were intermixed in all conditions, 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 sclerosing cholangitis from autoimmune hepatitis (P = 0.0007) and primary biliary cirrhosis (P = 0.00007) and DR3 distinguished autoimmune hepatitis (P = 0.002) and primary sclerosing cholangitis (P = 0.0005) from primary biliary cirrhosis. Only the occurrence of DR4 in primary sclerosing cholangitis was lower than in normal subjects (P = 0.02). Patients with mixed genetic risk factors did not have distinctive features or manifestations of hybrid conditions. We conclude that patients with shared genetic risk factors do not have characteristic features nor do they have overlap syndromes. DR4 may be protective against primary sclerosing cholangitis.
Czaja
A J
AJ
Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Santrach
P J
PJ
Breanndan Moore
S
S
D000328:Adult; D001327:Autoimmune Diseases / Q000235:genetics*; D015209:Cholangitis, Sclerosing / Q000235:genetics*; D004198:Disease Susceptibility; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D059810:HLA-DR Serological Subtypes; D015803:HLA-DR3 Antigen / Q000032:analysis; D015804:HLA-DR4 Antigen / Q000032:analysis; D019693:Hepatitis, Autoimmune / Q000235:genetics*; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; D015803:HLA-DR3 Antigen; D015804:HLA-DR4 Antigen; C041559:HLA-DR8 antigen