Genetic susceptibility to Tardive Dyskinesia in chronic schizophrenia subjects: V. Association of CYP1A2 1545 C>T polymorphism.
Tardive dyskinesia (TD) is an iatrogenic disorder observed in approximately 20-30% of schizophrenia patients on long-term treatment with typical antipsychotic drugs. CYP1A2 is involved in the metabolism of atypical antipsychotic drugs such as clozapine and olanzapine. It is not directly involved in the metabolism of typical antipsychotic drugs, but gains importance when the schizophrenia patients are under long-term chronic treatment, acting as a low-affinity high-capacity metabolizing enzyme. In this study, we have completely sequenced the coding region to ascertain the presence of common coding polymorphisms and their role if any in susceptibility to TD and schizophrenia. Four previously reported polymorphisms, CYP1A2*1F (intron A), rs2472304 & rs3743484 (intron D) and rs2470890 (CYP1A2 1545 C>T) in exon 7 were identified. We further investigated whether the CYP1A2 1545 C>T polymorphism has any role to play in susceptibility to TD and in schizophrenia per se. Association of this single nucleotide polymorphism with TD (P=0.03) and schizophrenia (P=0.04) was observed, but was rendered insignificant after corrections for multiple comparisons.
Tiwari
A K
AK
Department of Genetics, University of Delhi South Campus, New Delhi, India.
Deshpande
S N
SN
Lerer
B
B
Nimgaonkar
V L
VL
Thelma
B K
BK
D014150:Antipsychotic Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D004252:DNA Mutational Analysis; D004409:Dyskinesia, Drug-Induced / Q000201:enzymology / Q000235:genetics*; D005091:Exons; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007438:Introns; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D016896:Treatment Outcome
D014150:Antipsychotic Agents; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2