Pharmacogenetics of tardive dyskinesia in schizophrenia:The role of CHRM1 and CHRM2 muscarinic receptors

OBJECTIVES: Acetylcholine M (muscarinic) receptors are possibly involved in tardive dyskinesia (TD). The authors tried to verify this hypothesis by testing for possible associations between two muscarinic receptor genes (CHRM1 and CHRM2) polymorphisms and TD in patients with schizophrenia.METHODS: A total of 472 patients with schizophrenia were recruited. TD was assessed cross-sectionally using the Abnormal Involuntary Movement Scale. Fourteen allelic variants of CHRM1 and CHRM2 were genotyped using Applied Biosystems amplifiers (USA) and the MassARRAY System by Agena Bioscience.RESULTS: The prevalence of the rs1824024*GG genotype of the CHRM2 gene was lower in TD patients compared to the group without it (χ2 = 6.035, p = 0.049). This suggested that this genotype has a protective effect for the development of TD (OR = 0.4, 95% CI: 0.19-0.88). When age, gender, duration of schizophrenia and dosage of antipsychotic treatment were added as covariates in regression analysis, the results did not reach statistical significance.CONCLUSIONS: This study did identify associations between CHRM2 variations and TD; the results of logistic regression analysis with covariates suggest that the association is, however, likely to be secondary to other concomitant factors.