Rana B K, Shiina T, Insel P A
Department of Pharmacology, University of California at San Diego, La Jolla, California 92093-0636, USA.
Annu Rev Pharmacol Toxicol. 2001;41:593-624. doi: 10.1146/annurev.pharmtox.41.1.593.
G protein-coupled receptors (GPCRs) represent a major class of proteins in the genome of many species, including humans. In addition to the mapping of a number of human disorders to regions of the genome containing GPCRs, a growing body of literature has documented frequently occurring variations (i.e. polymorphisms) in GPCR loci. In this article, we use a domain-based approach to systematically examine examples of genetic variation in the coding and noncoding regions of GPCR loci. Data to date indicate that residues in GPCRs are involved in ligand binding and coupling to G proteins and that regulation can be altered by polymorphisms. Studies of GPCR polymorphisms have also uncovered the functional importance of residues not previously implicated from other approaches that are involved in the function of GPCRs. We predict that studies of GPCR polymorphisms will have a significant impact on medicine and pharmacology, in particular, by providing new means to subclassify patients in terms of both diagnosis and treatment.
G蛋白偶联受体（GPCRs）是包括人类在内的许多物种基因组中的一类主要蛋白质。除了将许多人类疾病定位到含有GPCRs的基因组区域外，越来越多的文献记录了GPCR基因座中频繁出现的变异（即多态性）。在本文中，我们使用基于结构域的方法系统地研究GPCR基因座编码区和非编码区的遗传变异实例。迄今为止的数据表明，GPCRs中的残基参与配体结合和与G蛋白的偶联，并且多态性可以改变调节作用。对GPCR多态性的研究还揭示了以前从其他方法中未涉及的残基在GPCR功能中的功能重要性。我们预测，对GPCR多态性的研究将对医学和药理学产生重大影响，特别是通过提供新的方法在诊断和治疗方面对患者进行亚分类。
