Genomics and complex liver disease: Challenges and opportunities

Abstract

The concept of genetic susceptibility in the contribution to human disease is not new. What is new is the emerging ability of the field of genomics to detect, assess, and interpret genetic variation in the study of susceptibility to development of disease. Deciphering the human genome sequence and the publication of the human haplotype map are key elements of this effort. However, we are only beginning to understand the contribution of genetic predisposition to complex liver disease through its interaction with environmental risk factors. In the coming decade, we anticipate the development of human studies to better dissect the genotype/phenotype relationship of complex liver diseases. This endeavor will require large, well-phenotyped patient populations of each disease of interest and proper study designs aimed at answering important questions of hepatic disease prognosis, pathogenesis, and treatment. Teamwork between patients, physicians, and genomics scientists can ensure that this opportunity leads to important biological discoveries and improved treatment of complex disease. (HEPATOLOGY 2006;44:1380-1390

Twin studies in autoimmune disease: Genetics, gender and environment

“…Concordance rates in most conditions generally support both genetic and environmental influences, with varying degrees of each. These environmental factors include chemicals and xenobiotics, in some cases are related to lifestyle (alcohol, smoking, diet, exercise), as well as microorganisms [3]. A combination of environmental and genetic influences has formed the basis of a complex multi-hit model of disease, where a genetically predisposed individual encounters several environmental exposures over a lifetime, which culminate in disease development after a final series of crucial hits.…”

Genetics and Genomics of Primary Biliary Cirrhosis

“…Clustering of disease within families is often used as evidence of genetic influence on disease development as family members typically share more genetic material among themselves than with the general population, and thus are more likely to share genetic characteristics associated with increased risk of disease (14). It has long been appreciated that PBC aggregates in families, and the historical epidemiological studies have shown familial PBC prevalence (i.e.…”

Molecular Pathogenesis of Hepatitis-B-virus-associated Hepatocellular Carcinoma

“…SNPs on average appear approximately every 200 to 300 base pairs in the human genome, many of which cause functional changes by affecting transcription-factor binding sites, influencing splicing or stability of messenger RNA, or altering the amino acid sequence of the protein. 128,129 The outcomes of HBV infection do not appear to be determined by viral strains. Instead, allelic variants in human genome are likely to affect the viral hepatitis progression after infection.…”

“…Instead, allelic variants in human genome are likely to affect the viral hepatitis progression after infection. 129,130 Thus, it is conceivable that genetic differences significantly influence the progression of HBV infection. It has been reported that several genetic polymorphisms of TNF-α, IL-10, IL-6, TGF-β1, IGF-2, CTL antigen (CTLA)-4, and NFKB1A can influence the outcomes of chronic HBV infections.…”