Genetic association study between antipsychotic-induced weight gain and the melanocortin-4 receptor gene

被引：0
作者：
N I Chowdhury
A K Tiwari
R P Souza
C C Zai
S A Shaikh
S Chen
F Liu
J A Lieberman
H Y Meltzer
A K Malhotra
J L Kennedy
D J Müller
机构：
[1] Neurogenetics Section,Department of Neuroscience, Department of Psychiatry
[2] Centre for Addiction and Mental Health,Department of Neuroscience
[3] University of Toronto,Department of Psychiatry
[4] Laboratory of Neurosciences,undefined
[5] Graduate Program in Health Sciences Health Sciences Unit,undefined
[6] University of the Far South Catarinens,undefined
[7] Molecular Neuroscience,undefined
[8] Centre for Addiction and Mental Health,undefined
[9] University of Toronto,undefined
[10] College of Physicians and Surgeons,undefined
[11] Columbia University and the New York State Psychiatric Institute,undefined
[12] Psychiatric Hospital at Vanderbilt University,undefined
[13] Albert Einstein College of Medicine,undefined
[14] The Zucker Hillside Hospital,undefined
来源：
The Pharmacogenomics Journal | 2013年 / 13卷
关键词：
association study; clozapine; electrophoretic mobility-shift assays; MC4R; pharmacogenetics; weight gain;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
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 (r2⩽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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页码：272 / 279
页数：7
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