A functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene: association with tardive dyskinesia in schizophrenia

Basile, Vincenzo S.; Özdemir, Vural; Masellis, Mario; Walker, M.; Meltzer, Herbert Y.; Lieberman, Jeffrey A.; Potkin, Steven G.; Alva, Gustavo; Kalow, W.; Macciardi, Fabìo; Kennedy, James L.

doi:10.1038/sj.mp.4000736

Cited by 155 publications

(127 citation statements)

References 63 publications

(86 reference statements)

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“…15,18,29 However, it is similar to the frequency reported for African Americans. 15 Association of TD with CYP1A2*1F had earlier been reported by Basile et al 15 However, Schultze et al 20 failed to replicate this finding. In our population also we did not observe any significant association between TD and *1F.…”

Section: Association Of Cyp1a2 Polymorphisms With Tardive Dyskinesiasupporting

confidence: 83%

“…The lack of association could be attributed to several factors: (a) Differing genetic backgrounds as partly evident from differing allele frequencies in this gene; (b) The CYP1A2*1F (and also*1C) gene is inducible by smoking but smoking was not prevalent among schizophrenia subjects in our samples (however, CYP1A2 is induced by a variety of other substances such as glucosynolates present in cruciferous vegetable and charboiled meat); and (c) The sample size is small and thus reduced statistical power to detect any association if the gene is of minor effect (Table 2). However, since the sample characteristics with specific reference to prevalence of smoking were notably different from the previous reports, 15,20 any direct comparison between their observation and this study on ethnically distinct Indian population is inappropriate.…”

Section: Association Of Cyp1a2 Polymorphisms With Tardive Dyskinesiamentioning

confidence: 59%

“…Though CYP1A2 is considered to be a low-affinity high capacity metabolic clearance pathway for typical antipsychotics compared to CYP2D6, saturation of the latter during chronic long-term treatment makes CYP1A2 an important enzyme for antipsychotic metabolism. 15 Smoking is a potent inducer of CYP1A2 gene as is evident from the increased rate of caffeine biotransformation. A higher prevalence of smoking B80% 16 has been reported in schizophrenia subjects compared to B25% in the general population.…”

Section: Introductionmentioning

confidence: 99%

“…Nonsmoking subjects did not show any significant differences in the metabolic activity. In view of the above results, Basile et al (2000) investigated whether this mutation contributes to the risk of developing TD in chronic schizophrenia subjects. Abnormal Involuntary Movement Scale (AIMS 19 ) scores were used to assess the severity of TD among 85 schizophrenia subjects.…”

Section: Introductionmentioning

confidence: 99%

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Genetic susceptibility to Tardive Dyskinesia in chronic schizophrenia subjects: I. Association of CYP1A2 gene polymorphism

et al. 2004

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Understanding the pharmacogenetic basis of developing iatrogenic disorders such as Tardive Dyskinesia (TD) has significant clinical implications. CYP1A2, an inducible gene of the cytochrome P450 family of genes, has been suggested to contribute to the metabolism of typical antipsychotics in subjects with schizophrenia on long-term treatment, and has been considered as a potential candidate gene for development of TD. In this study, we have investigated the significance of CYP1A2 gene polymorphisms in TD susceptibility among chronic schizophrenia sufferers (n ¼ 335) from north India. TD was diagnosed in B29% (96/335) of these subjects. Of the 96 TD positives, 28 had been treated with typical antipsychotics alone, 23 with atypical antipsychotics alone and 45 patients had received both classes of drugs during the course of their illness. Out of the six SNPs tested, CYP1A2*2, *4, *5, *6 were found to be monomorphic in our population. CYP1A2*1C and CYP1A2*1F were polymorphic and were analyzed in the study sample. Since these two allelic variants lead to lesser inducibility among smokers, the smoking status of TD patients was also considered for all subsequent analysis. We observed increased severity of TD among TD-Y smokers, who were carriers of CYP1A2*1C (G4A) variant allele and had received only typical antipsychotic drugs (F(1,8) ¼ 9.203, P ¼ 0.016). No significant association of CYP1A2*1F with TD was observed irrespective of the class of drug they received or their smoking status. However, we found a significant association of CYP1A2*1F with schizophrenia (w 2 ¼ 6.572, df ¼ 2, P ¼ 0.037).

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Section: Association Of Cyp1a2 Polymorphisms With Tardive Dyskinesiasupporting

confidence: 83%

Section: Association Of Cyp1a2 Polymorphisms With Tardive Dyskinesiamentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Genetic susceptibility to Tardive Dyskinesia in chronic schizophrenia subjects: I. Association of CYP1A2 gene polymorphism

et al. 2004

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“…11 Additionally, CYP1A2 is induced by polycyclic aromatic hydrocarbons present in cigarette smoke and the reported alleles (marked in bold here) CYP1A2*1C (À3858G4A) and CYP1A2*1F (À163 A4C) lead to low induction in subjects who are smokers, thus influencing the bioavailability of antipsychotic drugs. [11][12][13] Previously, we had investigated the contribution of these two polymorphisms in the susceptibility to TD and did not observe any significant association with TD but observed an increased severity of TD in subjects carrying the A allele of the CYP1A2*1C polymorphism. 14 We had also investigated four other reported amino-acid substitutions in the coding region, but these were found to be monomorphic in our population.…”

Section: Ak Tiwari Et Almentioning

confidence: 99%

Genetic susceptibility to Tardive Dyskinesia in chronic schizophrenia subjects: V. Association of CYP1A2 1545 C>T polymorphism

Tiwari

Deshpande²,

Lerer

et al. 2006

Pharmacogenomics J

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Tardive dyskinesia (TD) is an iatrogenic disorder observed in B20-30% 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 C4T) in exon 7 were identified. We further investigated whether the CYP1A2 1545 C4T polymorphism has any role to play in susceptibility to TD and in schizophrenia per se. Association of this single nucleotide polymorphism with TD (P ¼ 0.03) and schizophrenia (P ¼ 0.04) was observed, but was rendered insignificant after corrections for multiple comparisons.

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Potential Role of Pharmacogenomics in Reducing Adverse Drug Reactions

Phillips

Veenstra

Oren

et al. 2001

JAMA

632

282

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A functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene: association with tardive dyskinesia in schizophrenia

Cited by 155 publications

References 63 publications

Genetic susceptibility to Tardive Dyskinesia in chronic schizophrenia subjects: I. Association of CYP1A2 gene polymorphism

Genetic susceptibility to Tardive Dyskinesia in chronic schizophrenia subjects: I. Association of CYP1A2 gene polymorphism

Genetic susceptibility to Tardive Dyskinesia in chronic schizophrenia subjects: V. Association of CYP1A2 1545 C>T polymorphism

Potential Role of Pharmacogenomics in Reducing Adverse Drug Reactions

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