Pharmacogenomics of GPCR Drug Targets Cell ( IF 30.41 ) Pub Date : 2017-12-14 , DOI: 10.1016/j.cell.2017.11.033 Alexander S. Hauser, Sreenivas Chavali, Ikuo Masuho, Leonie J. Jahn, Kirill A. Martemyanov, David E. Gloriam, M. Madan Babu
Natural genetic(遗传的) variation(变化) in the human genome(基因组) is a cause of individual(个人的) differences in responses to medications(药物) and is an underappreciated(未受到充分赏识的) burden(负担) on public health. Although 108 G-protein-coupled receptors(受体) (GPCRs) are the targets of 475 (～34%) Food and Drug Administration (FDA)-approved drugs and account for a global sales volume(量) of over 180 billion US dollarsannually(每年), the prevalence(流行) of genetic variation among GPCRs targeted by drugs is unknown. Byanalyzing(分析的) data from 68,496 individuals, we find that GPCRs targeted by drugs show genetic variation withinfunctional(功能的) regions such as drug- and effector-binding sites in the human population. Weexperimentally(实验的) show that certain variants(变体) of μ-opioid and Cholecystokinin-A receptors could lead to altered or adverse(不利的) drug response. By analyzing UK National Health Service drug prescription(药方) and sales data, we suggest that characterizing(描绘…的特性) GPCR variants could increase prescription precision(精度), improving patients’ quality of life, and relieve(解除) the economic(经济的) and societal(社会的) burden due tovariable(变量的) drug responsiveness(响应能力).
