期刊
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
卷 38, 期 2, 页码 134-141出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2012.03.001
关键词
Antipsychotic; Gene; Leptin; Leptin receptor; Polymorphism; Weight gain
资金
- NARSAD Young Investigator Award [MOP 89853]
- Abbott Labs
- ACADIA
- Bristol Myers Squibb
- Eli Lilly
- Janssen
- Pfizer
- Astra Zeneca
- Glaxo Smith Kline
- Memory
- Cephalon
- Minster
- Aryx
- BiolineRx
- Allon
- GlaxoSmithKline
- Merck
- Intracellular Therapies
- Novartis
- Psychogenics
- F. Hoffmann-LaRoche LTD
- Sepracor
- Targacept
Background: Antipsychotic-induced weight gain (AIWG) is a serious side-effect of antipsychotic medication leading to metabolic syndrome and increased cardiovascular morbidity. Unfortunately, there are still no valid predictors to assess an individual's risk to gain weight. Previous studies have indicated an impact of genetic variation in the genes encoding leptin, LEP, and leptin receptor, LEPR, on AIWG, but results have not been conclusive. Thus, we investigated polymorphisms in both genes for an association with AIWG. Methods: A total of 181 schizophrenic and schizoaffective patients treated with various antipsychotics were included. In a small subset of patients, leptin plasma levels were additionally obtained. Five polymorphisms in LEP and LEPR (LEP: rs7799039 (-2548G/A polymorphism), rs10954173, rs3828942; LEPR: rs1327120, rs1137101 (Q223R polymorphism) were genotyped using TaqMan assays. Statistical association with % weight change from baseline weight was performed using ANCOVA with baseline weight as covariate. Results: ANCOVA showed a non-significant trend for genotype association of the rs7799039 marker (p=.068). No significant association of the other LEP and LEPR SNPs with AIWG was detected. However, we found a significant association between a haplotype of LEP rs7799039G-rs10954173G-rs3828942G (p=.035) and AIWG. The rs7799039 G-allele (p=.042) and G-allele of rs3828942 (p=.032) were associated with higher weight gain. Conclusion: Our study supports the hypothesis of an impact of LEP gene variation on AIWG. Limitations of our study include heterogeneous samples, short treatment duration and multiple comparisons. Our findings were compared to previous studies in detail in order to provide the readers with a more conclusive picture. However, further studies are warranted including more gene variants and interaction analyses with other genes of the leptin-melanocortin pathway. (c) 2012 Published by Elsevier Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据