Interaction between polymorphisms of the dopamine D3 receptor and manganese superoxide dismutase genes in susceptibility to tardive dyskinesia

Objectives To investigate the influence of a functional polymorphism of the dopamine D3 receptor (DRD3), and assess its interaction with a Mn superoxide dismutase (MnSOD) polymorphism, in contributing to tardive dyskinesia in a chronic inpatient population with schizophrenia. Methods Chinese Han patients with schizophrenia were assessed for abnormal involuntary movements, and subgroups of 42 patients with persistent tardive dyskinesia and 59 consistently without dyskinesias were assessed for the DRD3 ser9gly and the MnSOD ala-9val polymorphisms. Results A higher, but not significant, frequency of DRD3 ser/gly heterozygotes was observed in the tardive dyskinesia group (0.52 versus 0.33, chi(2) = 5, degrees of freedom = 2, P = 0.08). However, assessment of the combined influence of the two polymorphisms demonstrated a significant effect (chi(2) = 8.09, degrees of freedom = 3, P = 0.04), whereby the combination of the MnSOD -9val and DRD3 9ser alleles was associated with tardive dyskinesia. Conclusions These results indicate a possible synergistic effect of genetic factors influencing mitochondrial free radical scavenging and dopamine receptor function on the susceptibility to tardive dyskinesia. (C) 2003 Lippincott Williams Wilkins.