Genetic variations and polymorphisms of G protein-coupled receptors: Functional and therapeutic implications

被引:74
作者
Rana, BK [1 ]
Shiina, T [1 ]
Insel, PA [1 ]
机构
[1] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA
关键词
SNPs; variants; mutants; structure-function; complex diseases;
D O I
10.1146/annurev.pharmtox.41.1.593
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:593 / 624
页数:34
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