Gagliano Sarah A, Tiwari Arun K, Freeman Natalie, Lieberman Jeffrey A, Meltzer Herbert Y, Kennedy James L, Knight Jo, Müller Daniel J
Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Hum Psychopharmacol. 2014 Jul;29(4):330-5. doi: 10.1002/hup.2407. Epub 2014 Apr 16.
Antipsychotics are effective in treating schizophrenia symptoms. However, the use of clozapine and olanzapine in particular are associated with significant weight gain. Mouse and human studies suggest that the protein kinase cAMP-dependent regulatory type II beta (PRKAR2B) gene may be involved in energy metabolism, and there is evidence that it is associated with clozapine's effects on triglyceride levels. We aimed at assessing PRKAR2B's role in antipsychotic-induced weight gain in schizophrenia patients.
DNA samples from adult schizophrenia or schizoaffective disorder patients of mixed ancestry were genotyped, and weight gain was assessed. We analyzed 16 tag single-nucleotide polymorphisms across the PRKAR2B gene in a Caucasian subset treated either with clozapine or olanzapine (N = 99). Linear regression based on an additive model was performed with the inclusion of relevant covariates.
Normalized per cent weight change was analyzed, revealing that patients with the minor allele at rs9656135 had a mean weight increase of 4.1%, whereas patients without this allele had an increase of 3.4%. This association is not significant after correcting for multiple testing.
Because of limited power, PRKAR2B's role in antipsychotic-induced weight gain is unclear, but biological evidence suggests that PRKAR2B may be involved. Further research in larger sample sizes is warranted.
抗精神病药物在治疗精神分裂症症状方面有效。然而，特别是氯氮平和奥氮平的使用与显著体重增加有关。小鼠和人体研究表明，蛋白激酶cAMP依赖性调节II型β（PRKAR2B）基因可能参与能量代谢，且有证据表明它与氯氮平对甘油三酯水平的影响有关。我们旨在评估PRKAR2B在精神分裂症患者抗精神病药物所致体重增加中的作用。
对成年混合血统的精神分裂症或分裂情感性障碍患者的DNA样本进行基因分型，并评估体重增加情况。我们在接受氯氮平或奥氮平治疗的白种人亚组（N = 99）中分析了PRKAR2B基因上的16个标签单核苷酸多态性。基于加性模型进行线性回归，并纳入相关协变量。
分析了标准化体重变化百分比，发现rs9656135位点携带次要等位基因的患者平均体重增加4.1%，而无此等位基因的患者体重增加3.4%。在进行多重检验校正后，这种关联不显著。
由于样本量有限，PRKAR2B在抗精神病药物所致体重增加中的作用尚不清楚，但生物学证据表明PRKAR2B可能参与其中。有必要在更大样本量上进行进一步研究。
