Pharmacogenomic Associations With Weight Gain in Olanzapine Treatment of Patients Without Schizophrenia

被引:19
作者
Houston, John P. [1 ,2 ]
Kohler, Jared [3 ]
Bishop, Jeffrey R. [4 ]
Ellingrod, Vicki L. [5 ,6 ]
Ostbye, Katherine M. [3 ]
Zhao, Fangyi [1 ]
Conley, Robert R. [1 ]
Hoffmann, Vicki Poole [1 ]
Fijal, Bonnie A. [1 ]
机构
[1] Eli Lilly & Co, Indianapolis, IN 46285 USA
[2] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN USA
[3] BioStat Solut Inc, Mt Airy, MD USA
[4] Univ Illinois, Dept Pharm Practice, Chicago, IL USA
[5] Univ Michigan, Dept Clin Social & Adm Pharm, Ann Arbor, MI 48109 USA
[6] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA
关键词
5-HT2C RECEPTOR GENE; SINGLE NUCLEOTIDE POLYMORPHISMS; BORDERLINE PERSONALITY-DISORDER; HYPOTHALAMIC NEUROPEPTIDE-Y; MAJOR DEPRESSIVE DISORDER; DOUBLE-BLIND; BODY-WEIGHT; HTR2C GENE; THE-759C/T POLYMORPHISM; PROMOTER REGION;
D O I
10.4088/JCP.11m06916
中图分类号
B849 [应用心理学];
学科分类号
040203 ;
摘要
Objective: 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. Method: 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. Results: 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. Conclusions: 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.
引用
收藏
页码:1077 / 1086
页数:10
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