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Semin Liver Dis 2011; 31(2): 208-214
DOI: 10.1055/s-0031-1276648
© Thieme Medical Publishers

Genetic Modifiers of Liver Injury in Hereditary Liver Disease

Aftab Ala1 , Michael Schilsky2
  • 1Centre for Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Frimley Park Hospital NHS Foundation Trust, Surrey, United Kingdom
  • 2Division of Digestive Diseases and Yale New Haven Transplantation Center, Yale University School of Medicine, New Haven, Connecticut
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Publication History

Publication Date:
02 May 2011 (online)

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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.

KEYWORDS

Alpha-1 antitrypsin deficiency - cystic fibrosis - hereditary hemochromatosis - hereditary liver disease - modifier genes - Wilson disease

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Aftab AlaM.D. F.R.C.P. 

Centre for Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Frimley Park Hospital NHS Foundation Trust

Portsmouth Road, Surrey GU16 7UJ, United Kingdom

Email: a.ala@nhs.net

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