Small Kersten M, Seman Carrie A, Castator Alex, Brown Kari M, Liggett Stephen B
Departments of Medicine and Molecular Genetics, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Room G062, Cincinnati, OH 45267-0564, USA.
FEBS Lett. 2002 Apr 10;516(1-3):253-6. doi: 10.1016/s0014-5793(02)02564-4.
Polymorphisms of G-protein coupled receptor (GPCR) genes are associated with disease risk and modification, and the response to receptor-directed therapy. Genomic sequencing ( approximately 1700 automated runs) from as many as 120 chromosomes from 60 multiethnic individuals was performed to confirm non-synonymous coding polymorphisms reported in the dbSNP database from 25 randomly selected GPCR genes. These polymorphisms were in regions of the receptors responsible for structural integrity, ligand binding, G-protein coupling and phosphoregulation. However, most of these putative polymorphisms could not be confirmed (false positive rate of 68%). Based on these results, we suggest that the variability of the superfamily is not well defined, and we caution against exclusive reliance on databases for selection of candidate GPCR polymorphisms for disease association and pharmacogenetic studies.
G蛋白偶联受体（GPCR）基因的多态性与疾病风险、疾病演变以及受体导向治疗的反应相关。我们对来自60名多民族个体的多达120条染色体进行了基因组测序（约1700次自动测序），以确认从25个随机选择的GPCR基因的dbSNP数据库中报告的非同义编码多态性。这些多态性存在于受体中负责结构完整性、配体结合、G蛋白偶联和磷酸调节的区域。然而，这些推定的多态性大多无法得到确认（假阳性率为68%）。基于这些结果，我们认为该超家族的变异性尚未得到很好的界定，并且我们提醒不要仅仅依赖数据库来选择用于疾病关联和药物遗传学研究的候选GPCR多态性。
