Rojnić Kuzman, Martina and Medved, Vesna and Božina, Nada and Hotujac, Ljubomir and Šain, Ivica and Bilušić, Hrvoje
The influence of 5-HT(2C) and MDR1 genetic polymorphisms on antipsychotic-induced weight gain in female schizophrenic patients.
Psychiatry Research, 160 (3).
ISSN 0165-1781 (Print)
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.
||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
||Katedra za psihijatriju i psihološku medicinu
|Rojnić Kuzman, Martina||UNSPECIFIED|
||30 September 2008
||09 Oct 2008
||23 Sep 2011 16:10
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