7 The inheritance of alcoholic liver disease

Available evidence supports the concept that alcoholic liver disease (ALD) is a multifactorial disease with a heritable component. A number of polymorphic genes with small and additive effects will thus encode susceptibility to this ‘polygenic’ disease. Molecular genetic studies of ALD are in their infancy, and methods available for the genetic dissection of complex traits are discussed. Some candidate genes have been identified, and studies have been undertaken to test for association between specific alleles and ALD susceptibility. There is evidence to support a role for alleles of two genes encoding enzymes involved in the oxidative metabolism of alcohol (acetaldehyde dehydrogenase2∗2 and cytochrome P4502E1 c2 allele) in susceptibility to ALD. More recently, attention has focused on cytokines, and there are now data showing association of specific alleles of both tumour necrosis factor alpha and interleukin-10 with predisposition to ALD. These candidate genes need to be subjected to rigorous evaluation in different populations. Such research should help to define more precisely the molecular mechanisms underlying the development of ALD in a sub-population (<20%) of alcoholics, thereby improving the hepatologist's ability to develop rational treatments.