Neurogenetics Section, Department of Neuroscience, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Pharmacogenomics J. 2013 Jun;13(3):272-9. doi: 10.1038/tpj.2011.66. Epub 2012 Feb 7.
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.
抗精神病药引起的体重增加（AIWG）可能导致精神分裂症（SCZ）患者出现代谢综合征。黑皮质素-4 受体（MC4R）基因的下游变体与各种人群的肥胖有关。因此，我们研究了 MC4R 区域的单核苷酸多态性（SNP）与 SCZ 患者 AIWG 的关联。对 224 名接受 SCZ 治疗并接受长达 14 周 AIWG 评估的患者进行了 4 个 SNP（rs2229616、rs17782313、rs11872992 和 rs8087522）的基因分型。我们使用协方差分析比较了三个 SNP（r²≤0.8）的基因型组之间的体重变化（%）。氯氮平上 rs8087522 A 等位基因携带者（AG+AA）的欧洲血统患者体重增加明显多于非携带者（P=0.027，n=69）。经过多次检验校正后，这些观察结果变得微不足道。我们进行了体外电泳迁移率变动分析，表明 A 等位基因的存在可能创建了转录因子结合位点。需要进一步研究这两个探索性发现。
