Polymorphisms of the ABCB1 Gene are Associated with the Therapeutic Response to Risperidone in Chinese Schizophrenia Patients

Abstract

P-glycoprotein, a product of the ATP-binding cassette B1 (ABCB1) gene, plays an important role in absorption and distribution of drugs. The brain entry of risperidone and 9-OH-risperidone is greatly limited by P-glycoprotein, which implies that the functional polymorphisms of ABCB1 in humans may be a factor contributing to the variability in response to risperidone. The present study was therefore designed to examine whether polymorphisms of the ABCB1 gene are related to therapeutic response. For this purpose, 130 Chinese schizophrenia patients undergoing risperidone treatment were recruited. Plasma drug concentrations were monitored and clinical symptoms were evaluated using the Brief Psychiatric Rating Scale (BPRS) before and 8 weeks after the treatment. Association tests between genotypes and percentage improvement in total BPRS scores were performed using analyses of variance. Our results show that genotyping C1236T may help to predict the efficacy of risperidone treatment on the basis that patients with the TT genotype showed greater improvement than those with other genotypes on the overall BPRS (F = 3.967, p = 0.021), while other polymorphisms, including rs13233308, G2677T/A and C3435T polymorphism, did not show any association with the response to risperidone. These results showed suggestive evidence that genetic variation in the ABCB1 gene may influence the individual response to risperidone.

Pharmacogenetics of risperidone therapy in autism: association analysis of eight candidate genes with drug efficacy and adverse drug reactions

“…40 Our results show that the ABCB1 c.1236C4T polymorphism influences risperidone clinical improvement, with patients carrying the T allele showing better improvement, in agreement with an earlier study. 41 The 1236T allele, which has been associated with lower expression and function of P-glycoprotein in the blood-brain barrier and in the small intestine, [42][43][44] would lead to a lower efflux of risperidone and hence higher drug concentration in the brain, therefore explaining the better outcome of the patients carrying this allele. The silent Abbreviations: EM, extensive metabolizers; PM, poor metabolizers, UM, ultra-rapid metabolizers.…”

Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight

“…A naturalistic study by Vijayan et al found that individuals with 3435CC (rs1045642) and 1236CC (rs1128503) genotypes responded better to a variety of APs, using the BPRS scale (93). Notably, earlier monotherapy studies in other populations found that individuals with the 3435TT genotype showed better response to olanzapine (94), and those with the 1236TT polymorphism showed better response to risperidone (95). On the contrary, Crisafulli et al did not observe an association between ABCB1 and response in a Korean population treated with a variety of APs using the PANSS scale (96).…”

Genetic variants in the BDNF gene and therapeutic response to risperidone in schizophrenia patients: a pharmacogenetic study

“…[5][6][7][8][9][10] A total of 127 unrelated schizophrenia patients (45 males and 84 females; mean±SD age: 36.1±11.1 years) were recruited from the Shanghai Mental Health Center on the basis of the following inclusion criteria: (1) had no physical complications or other psychiatric disorders; (2) had no history suggesting that antipsychotic treatment would be ineffective; (3) satisfied the DSM-IV criteria for schizophrenia; and (4) had not received any medication for 4-6 weeks before this study. All subjects gave signed, written informed consent through their responsible relatives before the study.…”

“…3,4 Genetic factors are commonly considered to be the main cause of these interindividual differences. [5][6][7][8][9][10] Previous studies have demonstrated that the expression levels of the human brain-derived neurotrophic factor (BDNF) gene in the prefrontal cortex, hippocampus are decreased in schizophrenic patients. 11 Clinical psychopharmacological and animal model-based experiments have also shown that antipsychotics can regulate the expression of BDNF.…”