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

Abstract

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=335) from north India. TD was diagnosed in ~29% (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 (G>A) variant allele and had received only typical antipsychotic drugs (F(1,8)=9.203, P=0.016). No significant association of CYP1A^*21F 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 (χ²=6.572, df=2, P=0.037).