The correlation between CYP2D6 gene polymorphisms and clinical response of risperidone treatment in Chinese Han schizophrenia patients

Abstract

Objective To investigate the relationship between the polymorphisms of CYP2D6 gene and clinical efficacy of risperidone in schizophrenia. Methods 114 schizophrenia patients were recruited and completed 12 weeks of treatment with risperidone monotherapy. Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance Scale (PSP), Digit Span Test in Wechsler Intelligence Scale, Raven's Standard Progressive Matrices, Digital Cancellation Test were used to assess patients 'psychotic symptoms and cognitive symptom, and all patients were evaluated at baseline and weekend of 12. 178 healthy controls were also collected. Five SNPs (rs1065852, rs1135840, rs16947, rs1080985, rs5030655) in CYP2D6 were genotyped by using TaqMan® SNP Genotyping Assays. SHEsis online software were used to detect the Hardy-Weinberg equilibrium, pairs of polymorphic loci linkage disequilibrium, genotype and allele frequency analysis and haplotype analysis. SPSS17.0 statistical package was used for statistical analysis. Results rs5030655 was found only homozygous, suggesting not polymorphic site. Schizophrenia and control groups were not statistically different in genotype distributions and allele frequencies of four polymorphic sites (P>0.05). There was a strong linkage disequilibrium between rs16947 and rs1080985 (r2=0.655) . Haplotype frequency of three SNPs rs16947/rs1065852/rs1080985 AGG in schizophrenia group was significantly greater than in healthy people (14.26 vs. 7.07; χ2=8.008, P=0.004). At baseline, CC patients of rs1135840 genotype scored less than CG and GG genotype patients in Raven's Standard Progressive Matrices (F=3.205, P 0.05) . After treatment, AA patients of rs16947 genotype had smallest score changes in Digital Cancellation Test (F=3.249, P=0.043) , the results still showed statistical significance after Bonferroni corrections (P=0.022, 0.042), and there was no statistical significant difference between the genotype GG and AG (P>0.05) . Conclusions There is no relationship between the polymorphism of CYP2D6 gene and the susceptibility of schizophrenia, but rs1135840 may be associated with intellectual impairment at baseline and improvement after treatment in patients with schizophrenia. rs16947 may be associated with improved attention in the treatment of schizophrenia. Key words: Schizophrenia; Cytochrome P-450 CYP2D6; Treatment outcome; Risperidone