title: Associations between MDR1 gene polymorphisms and schizophrenia and therapeutic response to olanzapine in female schizophrenic patients.
abstract: Multidrug resistant protein (MDR1) gene, which codes for P-glycoprotein and functions as an efflux transporter in different cells, is widely localized in normal tissues including the gastrointestinal tract, blood cells, biliary tract, kidney and brain and plays a major role in absorption, distribution and elimination of various xenobiotics. Therefore, MDR1 gene variants were proposed as potential susceptibility factors for diseases and as determinants of treatment response to various drugs. We investigated the relationships between exon 21 G2677T and exon 26 C3435T genetic variants of MDR1 gene with susceptibility and treatment response in female schizophrenic patients. The study was conducted in two steps. We first compared allele, genotype and haplotype distributions between 117 female schizophrenic patients and 123 control female subjects. Afterwards, we studied treatment response to olanzapine, in 87 out of 117 previously unmedicated female patients. Overall, we found lower representation of G2677/C3435 haplotype in schizophrenic female patients compared to controls. Test result for linkage disequilibrium between loci was found to be significant. Furthermore, we found significant associations between MDR1 exon 21 G2677T genotypes and treatment response measured with positive PANSS percentage changes, with T allele and TT genotype being associated with significantly better treatment response. A borderline, non-significant statistical association was found between MDR1 exon 26 C3435T genotypes and treatment response, with TT genotype being associated with better treatment response. Our data support functional importance of the MDR1 mutations for the susceptibility and treatment response in female schizophrenic patients.
authors.affiliation: Clinical Institute of Laboratory Diagnosis, Zagreb University Hospital Centre, Salata 2, 10000 Zagreb, Croatia. nbozina@net.hr
authors.forename: Nada
authors.initials: N
authors.lastname: Bozina
authors.forename: Martina Rojnic
authors.initials: MR
authors.lastname: Kuzman
authors.forename: Vesna
authors.initials: V
authors.lastname: Medved
authors.forename: Nikolina
authors.initials: N
authors.lastname: Jovanovic
authors.forename: Jadranka
authors.initials: J
authors.lastname: Sertic
authors.forename: Ljubomir
authors.initials: L
authors.lastname: Hotujac
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D000077152:Olanzapine; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D012016:Reference Values; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000077152:Olanzapine