CYP2D6 genetic polymorphism and genetic ancestry on extrapyramidal side-effects of long-term treatment with classical antipsychotics in cuban patients with schizophrenia

Author(s): Hilda Roblejo Balbuena, Beatriz Marcheco Teruel, Salvador González Pal, Toro Bordado, Ivette Camayd Viera, Giselle Monzón Benítez, Lilia C Marín Padrón, Adrián Llerena Ruíz

Background: Different factors alter a patient’s susceptibility to adverse neuroleptic reactions. The CYP2D6 gene codes for a human cytochrome P450 2D6 enzyme, which is responsible for the metabolism of many psychiatric drugs. Ethnicity may also influence the susceptibility to adverse effects of long-term treatment with classical Antipsychotics (AP) because allele frequencies differ in correspondence with interethnic differences.

Objective: To evaluate whether the CYP2D6 allelic variants/predicted metabolic capacity status and the genetic ancestry are associated with classical antipsychotic-induced extrapyramidal side-effects (EPS) in Cuban patients with schizophrenia.

Methods and findings: A cross-sectional study was carried out. 209 patients were included: 61 of them with EPS at present and 148 patients without EPS. DNA samples were genotyped to estimate of admixture proportions and CYP2D6 genotype. Homozygous patients with non-functional alleles have a higher risk of developing EPS (RR=3.418). These patients have a higher proportion of European genes (0.82).

Conclusion: The Poor Metabolizer (PM) genotype may be a predisposing factor for EPS. The study did not find evidence that ethnic differences played a large part in the risk of EPS.