title: Genetic modifiers of liver injury in hereditary liver disease.
abstract: The genetic background of patients with liver diseases modulates hepatic injury, with some individuals being predisposed to better defenses and regenerative capacity. In this review, we focus our description of this phenomenon on inherited disorders affecting the liver, with a particular emphasis on Wilson disease (WD), genetic hemochromatosis, and α-1 anti-trypsin disease (A1-AT). Wide variations in the clinical phenotype of WD may in part be related to the mutations of the ATP7B genotype, though modifier genes and environmental factors also likely play an important role. There is also a significant variability in the expression of iron overload in patients with genetic hemochromatosis that are homozygous for the C282Y mutation. Homozygosity for the A1-ATZ mutation is generally required for the development of liver disease in A1-AT although there is increasing evidence for modifier effects from a heterozygous genotype in other liver diseases.
authors.affiliation: Centre for Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Frimley Park Hospital NHS Foundation Trust, Surrey, United Kingdom. a.ala@nhs.net
authors.forename: Aftab
authors.initials: A
authors.lastname: Ala
authors.forename: Michael
authors.initials: M
authors.lastname: Schilsky
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics; D000073840:Copper-Transporting ATPases; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D006432:Hemochromatosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000071020:Hemochromatosis Protein; D006527:Hepatolenticular Degeneration / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D040941:Heredity; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D008099:Liver / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics; D010641:Phenotype; D012720:Severity of Illness Index; D000515:alpha 1-Antitrypsin / Q000235:genetics; D019896:alpha 1-Antitrypsin Deficiency / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
chemical_list: D027682:Cation Transport Proteins; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases