Association of multidrug resistance 1 gene polymorphism with the clinical efficacy of paliperidone and risperidone in schizophrenic patients

Objective To explore the association between multidrug resistance 1gene (MDR1)polymorphisms with the therapeutic efficacy of paliperidone (9-hydroxyrisperidone) and risperidone in Han Chinese schizophrenic patients. Methods One hundred and thirty-three schizophrenic patients were given paliperidone or risperidone LAI for a 12-week treatment. The PANSS was used to assess the main therapeutic efficacy, and the Clinical Global Impression-Severity (CGI-S) scale and the Personal and Social Function scale (PSP) were used to as the secondary therapeutic efficacy assessments. The patients were evaluated every 2 weeks. The polymerase chain reaction-based-restriction fragment length polymorphisms (PCRRFLP) and DNA sequencing were used to detect the genotypes of 5 candidate single nucleotide polymorphisms (SNPs). The association between MDR1 genotypes with the therapeutic efficacy was analyzed using the chi-square and ANOVA tests. Results There were no statistical significant differences between MDR1 gene polymorphism and the PANSS reduction rate or clinical efficacy rate(P ＞0.05). Non-parameter tests revealed that, patients carrying CC genotype of locus rs1045642 had better efficacy in negative symptom item ' difficulty in abstract thinking' ( Z = - 2. 62, P = 0. 009 ) and positive symptom item ' grandiosity '(Z = -2. 84,P =0. 005), and GG genotype of locus rs2032582 carriers had worse improvements in general psychopathology item 'tension' (Z = -2.50,P =0. 012), and as to patient who carried A allele of locus rs1202169 had better improvements in general psychopathology item 'active societal avoidance'(Z = -2. 09,P =0. 036), and CC genotype of locus rs13233308 carriers had worse improvements in items ' guilt feelings' (Z = - 2. 09, P = 0. 036) and ' lack of spontaneity and flow of conversation' (Z = - 2.73,P = 0. 006) ,TT genotype carriers had a better improvement in item ' tension' ( Z = - 2. 54, P = 0. 011).Secondary clinical efficacy analysis showed that locus C allele of rs1045642 might be associated with patients' higher PSP score (Z = -2. 18, P = 0. 029). Conclusion MDR1 gene polymorphisms may be not associated with the therapeutic efficacy of paliperidone and risperidone in Han Chinese schizophrenic patients, but may influence the clinical improvements of 'delusion' or 'active societal avoidance' of schizophrenia, which maybe provide references for schizophrenic patients' individual drug therapy. Key words: Schizophrenia;  Multidrug resistance gene;  Polymorphism, restriction fragment length;  Risperidone;  Paliperidone