Genetics of Hepatobiliary Diseases

With the recent publication of the first human map of genetic variation (ie, Human Haplotype Map), genomic-based discoveries will likely affect not only the research bench but also the bedside. These advances will improve the understanding of the genetics of hepatobiliary diseases, resulting in better prevention measures and diagnosis as well as more effective therapies. Currently, alcoholic liver disease, nonalcoholic fatty liver disease, and symptomatic gallbladder stones affect a sizable portion of the population. On the other hand, chronic cholestatic liver diseases, hepatocellular carcinoma, and polycystic liver disease, although rare, shorten life expectancy and diminish the quality of life of patients. In the genomic era, we have the opportunity to start dissecting the susceptibility genetic variants of liver diseases. We are now in a position to begin elucidating the complex genotype/phenotype relationships of liver diseases with the anticipation to understand disease pathogenesis better. These efforts will require the application of genomic-based approaches in large well-organized translational studies in the diseases of interest.

Abbreviations used in this paper:  α1-AT, alpha 1 anti-trypsin , ADH, alcohol dehydrogenase , ADPKD, autosomal dominant polycystic kidney disease , ADPLD, autosomal dominant polycystic liver disease , ALD, alcoholic liver disease , AOR, adjusted odds ratio , CI, confidence interval , CTLA-4, cytotoxic T-lymphocyte antigen-4 , CYP7A1, cholesterol 7α-hydroxylase , DILI, drug-induced liver injury , ER, endoplasmic reticulum , GBS, gallbladder stones , HCC, hepatocellular carcinoma , MHC, major histocompatibility complex , NAFLD, nonalcoholic fatty liver disease , PBC, primary biliary cirrhosis , PCLD, polycystic liver disease , PSC, primary sclerosing cholangitis , ROS, reactive oxygen species