期刊
PHARMACOGENOMICS JOURNAL
卷 13, 期 3, 页码 272-279出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/tpj.2011.66
关键词
association study; clozapine; electrophoretic mobility-shift assays; MC4R; pharmacogenetics; weight gain
资金
- Abbott Labs
- ACADIA
- Bristol Myers Squibb
- Eli Lilly
- Janssen
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Memory
- Cephalon
- Minster
- Aryx
- BiolineRx
- Allon
- Forest Labs
- Merck
- Eli Lilly Corporation
- Canadian Institutes of Health Research (CIHR) [MOP 15007]
- Neurodevelopmental Genetics of Human Psychiatric Disorders [200508GMH]
- CIHR operating grant [MOP 89853]
- National Alliance for Research in Schizophrenia and Depression (NARSAD)
- OMHF New Investigator Fellowship [MH41468]
- Prentiss Foundation
- Ritter Foundation
- Hintz family
- Peterson Family
- Centre for Addiction and Mental Health postdoctoral fellowship
- National Alliance for Research in Schizophrenia and Depression Award (NARSAD)
- CIHR fellowship [XWY93967]
Antipsychotic-induced weight gain (AIWG) may result in the metabolic syndrome in schizophrenia (SCZ) patients. Downstream variants of the melanocortin-4 receptor (MC4R) gene have been associated with obesity in various populations. Thus, we examined single-nucleotide polymorphisms (SNPs) in the MC4R region for association with AIWG in SCZ patients. Four SNPs (rs2229616, rs17782313, rs11872992 and rs8087522) were genotyped in 224 patients who underwent treatment for SCZ and were evaluated for AIWG for up to 14 weeks. We compared weight change (%) across genotypic groups using analysis of covariance for three SNPs (r(2) <= 0.8). European-ancestry patients who were rs8087522 A-allele carriers (AG + AA) on clozapine gained significantly more weight than non-carriers (P = 0.027, n = 69). These observations were marginal after correction for multiple testing. We performed in vitro electrophoretic mobility-shift assay that suggested that the presence of the A-allele may create a transcription factor-binding site. Further investigation is warranted for both these exploratory findings.
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