Association study of polymorphisms in leptin and leptin receptor genes with antipsychotic-induced body weight gain
Association study of polymorphisms in leptin and leptin receptor genes with antipsychotic-induced body weight gain
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DOI：
10.1016/j.pnpbp.2012.03.001
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发表时间：
2012-08-07
影响因子：
5.6
通讯作者：
Puls, I.
中科院分区：
文献类型：
--
作者：
Brandl, E. J.;Frydrychowicz, C.;Puls, I.
背景资料：抗精神病药物引起的体重增加（AIWG）是抗精神病药物的严重副作用，可导致代谢综合征和心血管疾病发病率增加。不幸的是，仍然没有有效的预测指标来评估个人体重增加的风险。以前的研究表明，编码瘦素，LEP和瘦素受体，LEPR的基因的遗传变异对AIWG的影响，但结果尚未得出结论。因此，我们调查了这两个基因的多态性与AIWG.Methods：共181例精神分裂症和情感障碍患者接受各种抗精神病药物治疗。在一小部分患者中，另外获得了瘦素血浆水平。采用TaqMan技术对LEP和LEPR的5个多态性位点（LEP：rs7799039（-2548G/A多态性）、rs 10954173、rs3828942; LEPR：rs 1327120、rs 1137101（Q223 R多态性））进行基因分型。结果：ANCOVA显示rs7799039标记物的基因型关联的非显著趋势（p= 0.068）。其他LEP和LEPR SNPs与AIWG无显著关联。然而，我们发现LEP单倍型rs7799039 G-rs 10954173 G-rs3828942 G（p= 0.035）与AIWG之间存在显著关联。rs7799039的G等位基因（p=.042）和rs3828942的G等位基因（p=.032）与较高的体重gain.Conclusion：我们的研究支持LEP基因变异对AIWG的影响的假设。我们研究的局限性包括异质性样本，治疗时间短和多重比较。我们的研究结果与以前的研究进行了详细的比较，以便为读者提供一个更有说服力的图片。然而，进一步的研究是必要的，包括更多的基因变异和与瘦素-黑皮质素途径的其他基因的相互作用分析。(c)2012爱思唯尔公司出版
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.