Genetics and geoepidemiology of primary biliary cirrhosis: following the footprints to disease etiology

Abstract

The etiopathogenesis of primary biliary cirrhosis (PBC), an autoimmune disease characterized by the progressive destruction of intrahepatic bile ducts, is still enigmatic. There is growing evidence that suggests that the disease results from a combination of genetic and environmental factors. PBC should be regarded as a peculiar, yet representative autoimmune disease. For example, the relative risk for siblings and the concordance rate in monozygotic twins in PBC are among the highest reported in autoimmune conditions. Association studies for specific genes have provided weak associations, which often are limited to specific geographical areas. Interestingly, PBC epidemiology also presents a geographical pattern; it is more common in the northern parts of Europe and United States. In this article, we critically review available evidence regarding genetics and geoepidemiology in PBC. We also submit possible interpretations of data, new developments and theories, and attempt to indicate directions for future research efforts.