Interactive effect of cytochrome P450 17α-hydroxylase and dopamine D3 receptor gene polymorphisms on abnormal involuntary movements in chronic schizophrenia

Background: Tardive dyskinesia is a chronic adverse effect of anti psychotic drugs, where association with a polymorphic site in the dopamine D3 receptor gene has been previously reported. Cytochrome P 450 17α-hydroxylase activity has been implicated with modulation of central dopamine release as well as neuroprotection. We investigated the association of a T →C variation in the cytochrome P 450 17α-hydroxylase gene with tardive dyskinesia in patients with chronic schizophrenia. Methods: Cytochrome P 450 17 allele and genotype frequencies were compared between matched schizophrenia patients with (n = 55) or without tardive dyskinesia (n = 58). Interactive effects of cytochrome P 450 17α-hydroxylase with the dopamine D3 Ser9Gly polymorphism on abnormal involuntary movements were examined. Results: There was no difference in cytochrome P 450 17α-hydroxylase genotype distribution between patients with and without tardive dyskinesia; however, patients carrying the cytochrome P 450 17α-hydroxylase A2-A2 genotype and the dopamine D3gly allele had the highest orofacial (p< .04), distal (p< .05), and incapacitation (p< .04) scores on the Abnormal Involuntary Movements Scale. Conclusions: Schizophrenia patients who carry the dopamine D3gly allele and the cytochrome P 450 17α-hydroxylase A2-A2 genotype may be more likely to develop abnormal orofoacial and distal involuntary movements and to be incapacitated by these movements when chronically exposed to classical antipsychotic drugs.