Polymorphisms in human muscarinic receptor subtype genes.
A wide range of polymorphisms have been reported in muscarinic receptor subtype genes, mostly in M₁ and M₂ and, to a lesser extent, M₃ receptors. Most studies linking such genetic variability to phenotype have been performed for brain functions, but a more limited amount of information is also available for cardiac and airway function. Unfortunately, for none of the phenotypes under investigation a robust association with genotype has emerged. Moreover, it remains mostly unclear whether a reported association indicates a causative role of the polymorphism under investigation or merely a role as indicator of other polymorphisms affecting expression and/or function of the receptor. Also, most data on genotype-phenotype associations of muscarinic receptor subtypes are based on cross-sectional samples. Mechanistic studies linking polymorphisms to molecular, cellular, and tissue functions are largely missing. Finally, studies on a possible impact of muscarinic receptor polymorphisms on drug responsiveness are also largely missing. Thus, the field of genomics of muscarinic receptor subtypes is still in an early stage and a considerably greater number of studies will be required to judge the role of muscarinic receptor gene variability in physiology, pathophysiology, and drug treatment.
Department of Pharmacology and Pharmacotherapy, Academic Medical Center, University of Amsterdam, The Netherlands. Martin.michel@boehringer-ingelheim.com
Martin C
MC
Michel
Christine A
CA
Teitsma
D005838:Genotype; D006801:Humans; D010641:Phenotype; D011110:Polymorphism, Genetic; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*
D011976:Receptors, Muscarinic