Polymorphisms in Human Muscarinic Receptor Subtype Genes

Abstract

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.

Scientific opinion on the risks for animal and human health related to the presence of quinolizidine alkaloids in feed and food, in particular in lupins and lupin‐derived products

“…Separate genes encode these subtypes, which are expressed differently in the tissues (Carlson and Kraus, 2018). There are also polymorphisms in both nAChR and mAChR (Michel and Teitsma, 2012;Deflorio et al, 2017).…”

Genetic Polymorphism of CHRM2 in COPD: Clinical Significance and Therapeutic Implications

“…Several different beta-adrenergic and cholinergic muscarinic receptor exhibit genetic polymorphisms that were studied in asthma and in COPD. Furthermore, their contribution to the burden of airways disease in the population is uncertain (Costello et al, 1998;Donfack et al, 2003;Hizawa et al, 2007;Vacca et al, 2009;Michel and Teitsma, 2012;Thomsen et al, 2012;Jung et al, 2011). Among the different polymorphisms studied the CHRM2 has shown interesting results.…”

“…A dysfunctional M2 receptor might not effectively exercise its action, with an accumulation of Ach in the synaptic cleft, and consequent bronchoconstriction (Costello et al, 1998). Some studies have shown the existence of polymorphisms of genes of the receptors b2-adrenergic and muscarinic M2 and M3 receptors involved in the control of bronchomotor tone (Donfack et al, 2003;Hizawa et al, 2007;Szczepankiewicz et al, 2009;Vacca et al, 2009;Michel and Teitsma, 2012;Thomsen et al, 2012). The effects of these polymorphisms may be responsible of the different receptor responses to bronchodilators.…”

Pharmacogenetics of tardive dyskinesia in schizophrenia: The role ofCHRM1andCHRM2muscarinic receptors

“…DNA concentrations were measured with a Thermo Scientific NanoDrop 8000 UV-Vis Spectrophotometer. Possibly relevant SNPs were selected according to the literature data on associations with schizophrenia and other mental disorders (Cohen-Woods et al 2009;Jagannathan et al 2010;Michel and Teitsma 2012;Miyauchi et al 2016) and programme LD TAG SNP Selection (TagSNP).…”