Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technischen Universität München, München, Germany.
Klinik für Psychiatrie und Psychotherapie, Klinikum rechts der Isar, Technischen Universität München, München, Germany.
Pharmacopsychiatry. 2019 Jan;52(1):16-23. doi: 10.1055/s-0043-125392. Epub 2018 Jan 15.
Weight gain is a limiting and frequent adverse effect of second-generation antipsychotic therapy. Identifying genetic risk factors would significantly improve pharmacotherapy.
We focused on rs7185735 and rs9939609, 2 common single nucleotide polymorphisms of the fat mass and obesity-associated (FTO) gene reported to be associated with obesity. Three-hundred fifty Caucasian inpatients were included in a naturalistic study.
After 4 weeks of treatment, we did not observe any significant association of polymorphisms with weight change in the whole study population (p>0.05). In a subpopulation without additional weight-inducing comedication (n=178), G-allele carriers of rs7185735 gained 3.4 times more weight (1.69 kg±3.1 kg, p=0.019) than AA genotypes (0.49 kg±3.1 kg). A-allele carriers of rs9939609 gained 3.1 times more weight (1.65 kg±3.1 kg, p=0.029) than TT genotypes (0.54 kg±3.2 kg).
Our findings confirm the role of the FTO gene as a high-potential risk factor for obesity and indicate a value for predicting a weight gain induced by second-generation antipsychotics. Further, we detected an additive effect of FTO rs7185735 and MC4R rs17782313.
体重增加是第二代抗精神病药物治疗的一种常见且具有限制的不良反应。确定遗传风险因素将显著改善药物治疗。
我们主要关注与肥胖相关的脂肪质量和肥胖相关（FTO）基因的两个常见单核苷酸多态性 rs7185735 和 rs9939609。在一项自然主义研究中，纳入了 350 名高加索住院患者。
在治疗 4 周后，我们没有观察到多态性与整个研究人群体重变化之间存在任何显著关联（p>0.05）。在没有其他导致体重增加的合并药物治疗的亚组（n=178）中，rs7185735 的 G 等位基因携带者体重增加了 3.4 倍（1.69kg±3.1kg，p=0.019），而 AA 基因型体重仅增加 0.49kg±3.1kg。rs9939609 的 A 等位基因携带者体重增加了 3.1 倍（1.65kg±3.1kg，p=0.029），而 TT 基因型体重仅增加 0.54kg±3.2kg。
我们的研究结果证实了 FTO 基因作为肥胖的高潜力风险因素的作用，并表明了预测第二代抗精神病药物引起的体重增加的价值。此外，我们还检测到 FTO rs7185735 和 MC4R rs17782313 的附加效应。
