Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str 22 81675 München, Germany.
Int J Neuropsychopharmacol. 2013 Oct;16(9):2103-9. doi: 10.1017/S1461145713000849. Epub 2013 Aug 7.
Weight gain is a therapy limiting and very frequent adverse effect of many second-generation antipsychotic (SGA) drugs. The human melanocortin four receptor (MC4R) is a very promising candidate gene possibly influencing SGA-related weight gain. The rs489693 polymorphism near the MC4R gene was associated with SGA-related weight gain in a genome-wide association study. We tried to replicate these results in our independent naturalistic study population. From 341 Caucasian inpatients receiving at least one SGA drug (olanzapine, clozapine, risperidone, paliperidone, quetiapine or amisulpride), carriers homozygous for the rs489693 A-allele (n = 35) showed a 2.2 times higher weight increase (+2.2 kg) than carriers of the CC-genotype (+1 kg) after 4 wk of treatment (analysis of covariance, p = 0.039). We revealed an even stronger effect in a subpopulation without weight gain inducing co-medication (factor 3.1, +2.8 kg, p = 0.044, (n = 16 of 169)) and in first episode patients (factor 2.7, +2.7 kg, p = 0.017, (n = 13 of 86)). Our results confirm the rs489693 A-allele as a possible risk factor for SGA-related weight gain.
体重增加是许多第二代抗精神病药物（SGA）治疗的限制和常见的不良反应。人类黑素皮质素 4 受体（MC4R）是一个很有前途的候选基因，可能影响 SGA 相关的体重增加。MC4R 基因附近的 rs489693 多态性与全基因组关联研究中的 SGA 相关体重增加有关。我们试图在我们独立的自然主义研究人群中复制这些结果。从 341 名接受至少一种 SGA 药物（奥氮平、氯氮平、利培酮、帕利哌酮、喹硫平或氨磺必利）治疗的白种人住院患者中，rs489693 A 等位基因纯合子携带者（n = 35）在治疗 4 周后体重增加（协方差分析，p = 0.039）比 CC 基因型携带者（+1 公斤）高出 2.2 倍。我们在没有引起体重增加的合并用药的亚人群中发现了更强的效果（因素 3.1，+2.8 公斤，p = 0.044，n = 16/169）和首发患者（因素 2.7，+2.7 公斤，p = 0.017，n = 13/86）。我们的结果证实 rs489693 A 等位基因是 SGA 相关体重增加的一个可能的危险因素。
