Introduction

While most metabolic diseases result from single gene defects or the direct action of a toxic agent, there are circumstances where disordered metabolism or exposure to toxic agents gives rise to diseases which have a distinct immune basis. Such diseases are unlikely to arise from a single gene and fall into the category of ‘complex’ diseases, involving one or more genes as well as additional factors. The classical examples of immune-mediated metabolic disease are immune–allergic drug reactions (e.g. co-amoxiclav-induced hepatic cholestasis or minocyclin-induced autoimmune hepatitis) and metabolic diseases where repeated exposures induce chronic inflammation (e.g. alcoholic cirrhosis). The clinical outcome following acute toxic injury may also be influenced by the immune response (e.g. the outcome of acute liver failure following paracetamol overdose). Immune response genes may also play a role in determining the extent and severity of liver involvement in a number of single gene disorders including cystic fibrosis and α-1-antitrypsin deficiency.

The immune response genes do not themselves cause disease, but specific genes may be considered as risk factors with a potential to increase (i.e. susceptibility genes) or reduce (i.e. resistance genes) the risk of disease. Genes may also determine the rate of disease progression and/or the severity of symptoms (i.e. the disease phenotype). It must be remembered that these genes are often present in a large number of nonaffected individuals in the population and most are not defective under normal circumstances.