Pharmacogenetics of antipsychotic-induced weight gain

Lett, T. A. and T. J. Wallace, et al. (2012). "Pharmacogenetics of antipsychotic-induced weight gain: review and clinical implications." Mol Psychiatry 17(3): 242-66.

目的：明确截止到２０１２年抗精神药物引起的肥胖相关研究进展

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Pharmacokinetic药代动力学研究

• 影响血药浓度的基因可能影响体重

1. 如CYP450家族：CYP2D6，The 188T allele of CYP2D6 was significantly associated with AIWG in a study of Han Chinese SCZ patients undergoing risperidone treatment.

Lane H-Y, Liu Y-C, Huang C-L, Chang Y-C, Wu P-L, Lu C-T et al.
Risperidone-related weight gain: genetic and nongenetic
predictors. J Clin Psychopharmacol 2006; 26: 128–134.

2. MDR1编码P-糖蛋白，是ATP依赖的离子泵，在药物吸收方面起作用。The T alleles of the C2677T and C3435T polymorphisms were significantly associated with weight gain in risperidone- and olanzapine-treated women (P = 0.015 and P = 0.031, respectively)

Kuzman MR, Medved V, Bozina N, Hotujac L, Sain I, Bilusic H.
The influence of 5-HT(2C) and MDR1 genetic polymorphisms on antipsychotic-induced weight gain in female schizophrenic
patients. Psychiatry Res 2008; 160: 308–315.

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Pharmacodynamics药效动力学

• 单胺类物质影响机体平衡
  1、Serotonin system 5-羟色胺系统。
  许多抗精神疾病药物（SGAs）都是5-羟色胺受体的拮抗剂，它控制人体食欲，氟苯丙胺（d-fenfluramine）可以抑制食欲。很多研究表明HTR2C基因与体重相关。The rs3813929 (C/T) promoter SNP (�759C/T) of the X-linked HTR2C gene是最可能的与肥胖相关分子标记. 2006以来, 15 studies of 12 polymorphisms in four 5-HT receptor genes (namely HTR1A, HTR2A, HTR2C and HTR6) have been reported. HTR2C 另外一个启动子变异 rs518147 (�697C/G) and the combined haplotype (c.1-11429(GT)n 13 repeat (13R), �759C/T and 401C > G) were associated with the risk of obesity and metabolic syndrome。

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服用利培酮和氯氮平病人发现rs1414334C allele of the HTR2C gene与代谢综合征相关。102T/C polymorphism of the HTR2A gene，

2. 多巴胺系统（dopamine）
   靶向多巴胺与阳性症状改善相关

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DRD2 gene found that the C allele of rs4436578 与体重相关
3、 肾上腺能受体系统（adrenergic ）
与认知和情感功能相关
4、 组胺系统（histamine）
5、The G-protein system.
6、 食欲调控：Leptin瘦素