The influence of 5-HT(2C) and MDR1 genetic polymorphisms on antipsychotic-induced weight gain in female schizophrenic patients

Scientific paper - Original scientific paper

• Author: Martina Rojnić Kuzman
• Author: Vesna Medved
• Author: Nada Božina
• Author: Ljubomir Hotujac
• Author: Ivica Šain
• Author: Hrvoje Bilušić
• Author's institution: University of Zagreb; School of Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences

Abstract (english)

We investigated the relationships between functional genetic variants of the 5-HT(2C) receptor and multidrug-resistant protein (MDR1), coding for P-glycoprotein, and second generation antipsychotic (SDA)-induced weight gain among 108 female schizophrenic patients treated with olanzapine or risperidone for up to 4 months. No significant differences in -759C/T allelic and genotype variants of 5-HT(2C) were found between patients who gained more than 7% of their initial weight compared with those who gained less. Haplotype-based analysis of two MDR1 loci, exon 21 G2677T and exon 26 C3435T, revealed a slightly lower representation of the G2677/C3435 haplotype in the >/=7% group. In the subgroup of patients treated with risperidone, we found borderline overrepresentation of 2677T, significant overrepresentation of 3435T variant and borderline overrepresentation of 2677T/3435T haplotype the >/=7% group, whereas G2677/C3435 haplotype was found to be less represented in the >/=7% group. Our data indicate a nonsignificant role of 759C/T 5-HT(2C) in SDA-induced weight gain, and a stronger influence of the MDR1 G2677T and C3435T polymorphisms on risperidone-induced weight gain in female schizophrenic patients. 3435T and 2677T MDR1 variants, both associated with lower P-gp function, might predispose to higher risperidone accessibility to the brain that would lead to stronger effects, including weight gain.

• Keywords (english): Polymorphism, Genetic; Antipsychotic Agents - adverse effects - pharmacology - therapeutic use; Benzodiazepines - adverse effects - therapeutic use; Drug Resistance, Multiple - drug effects - genetics; Receptor, Serotonin, 5-HT2C - drug effects - genetics; Risperidone - adverse effects - therapeutic use; Schizophrenia - drug therapy - genetics; Weight Gain - drug effects - genetics; Adult; Exons - genetics; Female; Gene Frequency; Genes, MDR - drug effects - genetics; Genetic Predisposition to Disease; Genotype; Haplotypes - drug effects - genetics; Humans; Linkage Disequilibrium; Obesity - chemically induced; P-Glycoprotein - genetics; Polymorphism, Single Nucleotide; Promoter Regions, Genetic - genetics
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Accepted version
• Journal title: Psychiatry Research
• Numbering: vol. 160, no. 3, pp. 308-315
• p-ISSN: 0165-1781
• DOI: https://doi.org/10.1016/j.psychres.2007.06.006
• URN:NBN: urn:nbn:hr:105:833007
• Publication: 2008-09-30
• Document URL: https://doi.org/10.1016/j.psychres.2007.06.006
• Type of resource: Text
• Access conditions: Open access
• Created on: 2024-03-28 10:51:03