Allelic and somatic variations in the endogenous opioid system of humans.

People with a genetic predisposition for substance abuse have defects in genes for the opioid peptides and receptors. A high number of polymorphisms have been detected in the mu-opioid receptor, some of which result in pharmacological alterations. The opioid peptide proopiomelanocortin proved extraordinarily rich in mutations that often lead to severe phenotypical consequences. Prodynorphin displays a polymorphic regulation of transcription. Variants of the mu- and the delta-opioid receptor showed positive associations with opiate and/or alcohol addiction in some studies. However, these associations were weak, indicating a small contribution of the opioid system to these disorders.