Polymorphisms of the ABCB1 gene are associated with the therapeutic response to risperidone in Chinese schizophrenia patients.
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.
Xing
Qinghe
Q
Bio-X Center, Shanghai Jiao Tong University, Shanghai 200030, PR China.
Gao
Rui
R
Li
Huafang
H
Feng
Guoyin
G
Xu
Mingqing
M
Duan
Shiwei
S
Meng
Junwei
J
Zhang
Aiping
A
Qin
Shengying
S
He
Lin
L
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002681:China / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007555:Isoxazoles / Q000097:blood; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D027361:Organic Anion Transporters / Q000235:genetics*; D000068882:Paliperidone Palmitate; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D011743:Pyrimidines / Q000097:blood; D018967:Risperidone / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D012565:Schizophrenic Psychology
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014150:Antipsychotic Agents; D007555:Isoxazoles; D027361:Organic Anion Transporters; D011743:Pyrimidines; D018967:Risperidone; D000068882:Paliperidone Palmitate