Expression and therapeutic response related to apolipoprotein E polymorphism in primary biliary cirrhosis

Background/Aims/Methods: Apolipoprotein E polymorphism, affecting intestinal absorption and biliary secretion of bile acids, might also contribute to the variable course and response to drug treatment of primary biliary cirrhosis. To test this possibility, we studied the apo E gene frequency, and the expression and response to drug therapy in different apo E isoforms of 88 patients with primary biliary cirrhosis, randomized to ursodeoxycholic acid, colchicine or placebo treatments for 2 years. Results: The frequency of the 2 allele was 2.4 times higher (p<0.01) in the patients with primary biliary cirrhosis compared with the Finnish population. At entry the patients with the 4 allele were significantly younger (p<0.01) than those with other alleles, while the severity of primary biliary cirrhosis was similar in the three apolipoprotein E phenotypes. Liver enzymes, acute hepatic inflammation, serum total and low density lipoprotein cholesterol were decreased by ursodeoxycholic acid only in the patients with the 4 and homozygous 3 alleles, but not in those with the 2 allele. Improvements of liver enzyme tests by ursodeoxycholic acid were more marked in the patients with the 4 than other alleles. Conclusions: The present data show that in primary biliary cirrhosis the 2 allele is overrepresented, and suggest that the expression of primary biliary cirrhosis and response of the disease to ursodeoxycholic acid treatment are closely related to the apo E polymorphism.