The ACE gene I/D polymorphism does not affect the susceptibility to or prognosis of PBC

Primary biliary cirrhosis is an autoimmune liver disease that is strongly influenced by poorly defined, complex genetic factors. Alterations of the renin-angiotensin system have been implicated in the pathogenesis of various diseases. A deletion polymorphism of a 287-bp fragment of intron 16 of the angiotensin converting enzyme gene allele results in higher levels of circulating enzyme. Angiotensin converting enzyme deletion genotype has been linked to hypertension and sarcoidosis and has been reported to regulate liver fibrosis in HCV-mediated liver disease. We investigated the frequency of the Angiotensin converting enzyme gene insertion/deletion polymorphism in primary biliary cirrhosis patients.

52 biopsy-proven primary biliary cirrhosis patients and 98 healthy controls were evaluated. Angiotensin converting enzyme insertion/deletion polymorphism was detected by polymerase chain reaction amplification of a genomic DNA fragment on intron 16 of the angiotensin converting enzyme gene. Clinical phenotype of primary biliary cirrhosis was verified with positive anti-mitochondrial antibody or M2 antibody, demonstration of cholestatic liver enzymes, and staging of liver biopsy. The differences between these variables among different genotypes were noted.

There was no significant difference in genotypes and allele frequency between the primary biliary cirrhosis group and controls. The D allele frequency was 54% in primary biliary cirrhosis cases and 55% in controls (p=ns). Furthermore, there was no significant difference in clinical features between patients with angiotensin converting enzyme-insertion or insertion/deletion genotypes vs. patients with angiotensin converting enzyme-deletion genotype.

In our limited sample, the angiotensin converting enzyme deletion genotype did not make a significant contribution to the pathogenesis or progression of primary biliary cirrhosis.