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
