Interactive effect of cytochrome P450 17alpha-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 17alpha-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 17alpha-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 17alpha-hydroxylase with the dopamine D3 Ser9Gly polymorphism on abnormal involuntary movements were examined.


RESULTS
There was no difference in cytochrome P 450 17alpha-hydroxylase genotype distribution between patients with and without tardive dyskinesia; however, patients carrying the cytochrome P 450 17alpha-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 17alpha-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.
Segman
Ronnen H
RH
Biological Psychiatry Laboratory, Department of Psychiatry-Hadassah, Hebrew University Medical Center, Jerusalem, Israel.
Heresco-Levy
Uriel
U
Yakir
Avi
A
Goltser
Tanya
T
Strous
Rael
R
Greenberg
David A
DA
Lerer
Bernard
B
D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects; D002908:Chronic Disease; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D004409:Dyskinesia, Drug-Induced / Q000175:diagnosis / Q000209:etiology / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D050637:Receptors, Dopamine D3; D018009:Receptors, Glycine / Q000235:genetics / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D012720:Severity of Illness Index; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics* / Q000378:metabolism*
D014150:Antipsychotic Agents; C493593:DRD3 protein, human; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D018009:Receptors, Glycine; D003577:Cytochrome P-450 Enzyme System; D013254:Steroid 17-alpha-Hydroxylase