Department of Psychiatry, Kaiser Permanente San Francisco Medical Center, San Francisco, California.
Biol Psychiatry. 2015 Jan 1;77(1):29-35. doi: 10.1016/j.biopsych.2014.09.009. Epub 2014 Sep 23.
Clinicians already face "personalized" medicine every day while experiencing the great variation in toxicities and drug efficacy among individual patients. Pharmacogenetics studies are the platform for discovering the DNA determinants of variability in drug response and tolerability. Research now focuses on the genome after its beginning with analyses of single genes. Therapeutic outcomes from several psychotropic drugs have been weakly linked to specific genetic variants without independent replication. Drug side effects show stronger associations to genetic variants, including human leukocyte antigen loci with carbamazepine-induced dermatologic outcome and MC4R with atypical antipsychotic weight gain. Clinical implementation has proven challenging, with barriers including a lack of replicable prospective evidence for clinical utility required for altering medical care. More recent studies show promising approaches for reducing these barriers to routine incorporation of pharmacogenetics data into clinical care.
临床医生在每天面对“个体化”医学的同时,也在体验个体患者之间毒性和药物疗效的巨大差异。药物遗传学研究是发现药物反应和耐受性个体差异的 DNA 决定因素的平台。研究现在从分析单个基因开始,聚焦于基因组。几种精神药物的治疗结果与特定的遗传变异体相关,但没有独立的复制。药物副作用与遗传变异体的关联更强,包括与卡马西平诱导的皮肤病结局相关的人类白细胞抗原基因座和与非典型抗精神病药物体重增加相关的 MC4R。临床实施具有挑战性,包括缺乏可复制的前瞻性证据来证明改变医疗保健所需的临床实用性。最近的研究表明,有一些很有前途的方法可以减少这些障碍,从而将药物遗传学数据常规纳入临床护理。