Eli Lilly and Company, Indianapolis, Indiana, USA.
J Clin Psychiatry. 2012 Aug;73(8):1077-86. doi: 10.4088/JCP.11m06916.
Pharmacogenomic analyses of weight gain during treatment with second-generation antipsychotics have resulted in a number of associations with variants in ankyrin repeat and kinase domain containing 1 (ANKK1)/dopamine D2 receptor (DRD2) and serotonin 2C receptor (HTR2C) genes. These studies primarily assessed subjects with schizophrenia who had prior antipsychotic exposure that may have influenced the amount of weight gained from subsequent therapies. We assessed the relationships between single-nucleotide polymorphisms (SNPs) in these genes with weight gain during treatment with olanzapine in a predominantly antipsychotic-naive population.
The association between 5 ANKK1, 54 DRD2, and 11 HTR2C SNPs and weight change during 8 weeks of olanzapine treatment was assessed in 4 pooled studies of 205 white patients with diagnoses other than schizophrenia who were generally likely to have had limited previous antipsychotic exposure.
The A allele of DRD2 rs2440390(A/G) was associated with greater weight gain in the entire study sample (P = .0473). Three HTR2C SNPs in strong linkage disequilibrium, rs6318, rs2497538, and rs1414334, were associated with greater weight gain in women but not in men (P = .0032, .0012, and .0031, respectively). A significant association with weight gain for 2 HTR2C SNPs previously reported associated with weight gain, -759C/T (rs3813929) and -697G/C (rs518147), was not found.
Associations between weight gain and HTR2C and DRD2 variants in whites newly exposed to olanzapine may present opportunities for the individualization of medication selection and development based on differences in adverse events observed across genotype groups.
对第二代抗精神病药物治疗期间体重增加的药物基因组学分析导致了与锚蛋白重复和激酶结构域包含 1（ANKK1）/多巴胺 D2 受体（DRD2）和血清素 2C 受体（HTR2C）基因变异相关的许多关联。这些研究主要评估了有先前抗精神病药物暴露史的精神分裂症患者，这些患者可能会影响随后治疗期间体重增加的幅度。我们评估了这些基因中的单核苷酸多态性（SNP）与在主要未经抗精神病药物治疗的人群中使用奥氮平治疗期间体重增加之间的关系。
在四项针对 205 名非精神分裂症诊断患者的 pooled 研究中，评估了 5 个 ANKK1、54 个 DRD2 和 11 个 HTR2C SNP 与奥氮平治疗 8 周期间体重变化的关系，这些患者通常可能有有限的先前抗精神病药物暴露。
DRD2 rs2440390(A/G)的 A 等位基因与整个研究样本的体重增加相关（P =.0473）。三个紧密连锁的 HTR2C SNP（rs6318、rs2497538 和 rs1414334）与女性体重增加相关，但与男性无关（P =.0032、.0012 和.0031）。先前报道与体重增加相关的 2 个 HTR2C SNP（-759C/T(rs3813929)和-697G/C(rs518147)）与体重增加之间的显著关联未被发现。
在新接触奥氮平的白人中，体重增加与 HTR2C 和 DRD2 变异之间的关联可能为基于观察到的基因型组之间的不良反应差异来个体化药物选择和开发提供机会。
