| GENOMICS OF LIVER DISEASE
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| A few hepatic diseases arise due to single gene disorders and as such genetic techniques can identify those with a propensity to develop that disease or confirm the diagnosis in affected individuals.
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| Hereditary haemochromatosis is a genetically based disorder of iron metabolism, and is extremely common in northern Europeans, with a population prevalence of 1 in 200 to 1 in 300. Patients chronically absorb excessive amounts of iron from the gut, and tissue iron overload leads to multiorgan dysfunction, including cirrhosis of the liver. A transmembrane glycoprotein, known as HFE, modulates iron uptake and mutations in the genetic locus which encodes this protein, the HFE gene, underlie hereditary haemochromatosis. Two
point mutations, C282Y and H63D are found in the majority of those with hereditary haemochromatosis and can be identified easily by PCR-based assays. Alpha-1 antitrypsin (AA1T) deficiency leads to early onset lung disease and to liver cirrhosis. More than 90 allelic variants of the AA1T gene, at the so-called Pi or proteinase inhibitor locus, have been described, the majority of which do not affect plasma levels or activity of AA1T. Phenotypic variants in AA1T were initially described by their relative mobility on electrophoresis, with the most common variant, M, having medium mobility. The Z and S variants are most frequently associated with AA1T deficiency, and are both due to point mutations which can also be detected by PCR assays. Wilson's disease, another hereditary cause of cirrhosis due to excess copper deposition in the liver, is also caused by a single gene defect, but multiple mutations have been found in affected patients no routine assay is available for diagnosis.
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| Gilbert's disease (see below) is caused by a dinucleotide polymorphism in the TATA box promoter of the bilirubin UDP-glucuronyl transferase gene which impairs the hepatic uptake of unconjugated bilirubin.
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