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Muscarinic Receptors pp 49–59Cite as

Polymorphisms in Human Muscarinic Receptor Subtype Genes

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 208))

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.

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Notes

  1. 1.

    This manuscript refers to specific nucleotides by the single and specific amino acids by the three letter code. Where possible, we provide the rs identification number.

References

  • Anney RJL, Lotfi-Miri M, Olsson CA et al (2007) Variation in the gene coding for the M5 muscarinic receptor (CHRM5) influences cigarette dose but is not associated with dependence to drugs of addiction: evidence from a prospective population based cohort study of young adults. BMC Genet 8:46

    Article  PubMed  Google Scholar 

  • Brynne N, Dalen P, Alvan G et al (1998) Influence of CYP2D6 polymorphism on the pharmacokinetics and pharmacodynamics of tolterodine. Clin Pharmacol Ther 63:529–539

    Article  PubMed  CAS  Google Scholar 

  • Cannon DM, Klaver JK, Gandhi SK et al (2011) Genetic variation in cholinergic muscarinic-2 receptor gene modulates M2 receptor binding in vivo and accounts for reduced binding in bipolar disorder. Mol Psychiatry 16:407–418

    Article  PubMed  CAS  Google Scholar 

  • Cohen-Woods S, Gaysina D, Craddock N et al (2009) Depression case control (DeCC) study fails to support involvement of the muscarinic acetylcholine receptor M2 (CHRM2) gene in recurrent major depressive disorder. Hum Mol Genet 18:1504–1509

    Article  PubMed  CAS  Google Scholar 

  • Comings DE, Wu S, Rostamkhani M et al (2002) Association of the muscarinic cholinergic 2 receptor (CHRM2) gene with major depression in women. Am J Med Genet 114:527–529

    Article  PubMed  Google Scholar 

  • Comings DE, Wu S, Rostamkhni M et al (2003) Role of the cholinergic muscarinic 2 receptor (CHRM2) gene in cognition. Mol Psychiatry 8:10–13

    Article  PubMed  CAS  Google Scholar 

  • Detera-Wadleigh SD, Wiesch D, Bonner TI (1989) An SstI polymorphism for the human muscarinic acetylcholine receptor gene, m4 (CHRM 4). Nucleic Acids Res 17:6431

    Article  PubMed  CAS  Google Scholar 

  • Dick DM, Aliev F, Kramer J et al (2007) Association of CHRM2 with IQ: convering evidence for a gene influencing intelligence. Behav Genet 37:265–272

    Article  PubMed  Google Scholar 

  • Diefenbach K, Jaeger K, Wollny A et al (2008) Effect of tolterodine on sleep structure modulated by CYP2D6 genotype. Sleep Med 9:579–582

    Article  PubMed  Google Scholar 

  • Donfack J, Kogut P, Forsythe S et al (2003) Sequence variation in the promoter region of the cholinergic receptor muscarinic 3 gene and athma and atopy. J Allergy Clin Immunol 111:527–532

    Article  PubMed  CAS  Google Scholar 

  • Du Y, Remmers EF, Goldmuntz EA et al (1996) Linkage maps of rat chromosomes 15, 16, 17, 19, and X. Genomics 32:113–116

    Article  PubMed  CAS  Google Scholar 

  • Fenech AG, Ebejer MJ, Felice AE et al (2001) Mutation screening of the muscarinic M2 and M3 receptor genes in normal and asthmatic subjects. Br J Pharmacol 133:43–48

    Article  PubMed  CAS  Google Scholar 

  • Fenech AG, Billington CK, Swan C et al (2004) Novel polymorphisms influencing transcription of the human CHRM2 gene in airway smooth muscle. Am J Respir Cell Mol Biol 30:678–686

    Article  PubMed  CAS  Google Scholar 

  • Gosso MF, van Belzen M, de Geus EJC et al (2006) Association between the CHRM2 gene and intelligene in a sample of 304 Dutch families. Genes Brain Behav 5:577–584

    Article  PubMed  CAS  Google Scholar 

  • Gosso FM, de Geus EJC, Polderman TJC et al (2007) Exploring the functional role of the CHRM2 gene in human cognition: results from a dense genotyping and brain expression study. BMC Med Genet 8:66

    Article  PubMed  Google Scholar 

  • Greenwood PM, Lin M-K, Sundararajan R et al (2009) Synergistic effects of genetic variation in nicotinic and muscarinic receptors on visual attention but not working memory. Proc Natl Acad Sci USA 106:3633–3638

    Article  PubMed  CAS  Google Scholar 

  • Guggenheim JA, Zavats T, Hammond C et al (2010) Lumican and muscarinic acetylcholine receptor 1 gene polymorphisms associated with high myopia. Eye (Lond) 24:1411–1412

    Article  CAS  Google Scholar 

  • Hautala AJ, Rankinen T, Kiviniemi AM et al (2006) Heart rate recovery after maximal exercise is associated with acetylcholine receptor M2 (CHRM2) gene polymorphism. Am J Physiol 291:H459–H466

    CAS  Google Scholar 

  • Hautala AJ, Tulppo MP, Kiviniemi AM et al (2009) Acetylcholine receptor M2 gene variants, heart rate recovery, and risk of cardiac death after an acute myocardial infarction. Ann Med 41:197–207

    Article  PubMed  CAS  Google Scholar 

  • Hendershot CS, Bryan AD, Feldstein Ewing SW et al (2011) Preliminary evidence for associations of CHRM2 with substance use and disinhibition of adolescence. J Abnorm Child Psychol 39:671–681

    Article  PubMed  Google Scholar 

  • Janicky PK, Vealey R, Liu J et al (2011) Genome-wide association study using pooled DNA to identify candidate markers mediating susceptibility to postoperative nausea and vomiting. Anesthesiology 115:54–64

    Article  Google Scholar 

  • Jones KA, Porjesz B, Almasy L et al (2004) Linkage and linkage disequilibrium of evoked EEG oscillations with CHRM2 receptor gene polymorphisms: implications for human brain dynamics and cognition. Int J Psychophysiol 53:75–90

    Article  PubMed  Google Scholar 

  • Jung MH, Park BL, Lee BC et al (2011) Association of CHRM2 polymorphisms with severity of alcohol dependence. Genes Brain Behav 10:253–256

    Article  PubMed  CAS  Google Scholar 

  • Klett CP, Printz MP (1995) Is the M1-muscarinic recpetor a candidate gene for hypertension in the spontaneously hypertensive rat? Clin Exp Pharmacol Physiol 22(Suppl):S4–S6

    Article  CAS  Google Scholar 

  • Laramie JM, Wilk JB, Williamson SL et al (2009) Multiple genes influence BMI on chromosome 7q31-34: the NHLBI family heart study. Obesity 17:2182–2189

    Article  PubMed  Google Scholar 

  • Liao D-L, Hong C-J, Chen H-M et al (2003) Association of muscarinic M1 receptor genetic polymorphisms with psychiatric symptoms and cognitive function in schizophrenic patients. Neuropsychobiology 48:72–76

    Article  PubMed  CAS  Google Scholar 

  • Lin H-J, Wan L, Tsai Y et al (2009) Muscarinic acetylcholine receptor 1 gene polymorphisms associated with high myopia. Mol Vis 15:1774–1780

    PubMed  CAS  Google Scholar 

  • Lind PA, Luciano M, Horan MA et al (2009) No association between cholinergic muscarinic receptor 2 (CHRM2) genetic variation and cognitive abilities in three independent samples. Behav Genet 39:513–523

    Article  PubMed  Google Scholar 

  • Liu H-C, Hong C-J, Liu T-Y et al (2005) Association analysis for the muscarinic M1 receptor genetic polymorphisms and Alzheimer’s disease. Dement Geriatr Cogn Disord 19:42–45

    Article  PubMed  Google Scholar 

  • Lou X-Y, Ma JZ, Payne TJ et al (2006) Gene-based analysis suggests association of the nicotinic acetylcholine receptor β1 subunit (CHRNB1) and M1 muscarinic acetylcholine receptor (CHRM1) with vulnerability for nicotine dependence. Hum Genet 120:381–389

    Article  PubMed  CAS  Google Scholar 

  • Lucas JL, Sadee W, DeYoung JA (2001) Single nucleotide polymorphisms of the human M1 muscarinic acetylcholine receptor gene. AAPS PharmSci 3:57–61

    Article  Google Scholar 

  • Maeda Y, Hizawa N, Jinushi E et al (2006) Polymorphisms in the muscarinic receptor 1 gene confer susceptibility to asthma in Japanese subjects. Am J Respir Crit Care Med 174:1119–1124

    Article  PubMed  CAS  Google Scholar 

  • Mancama D, Arranz MJ, Landau S et al (2003) Reduced expression of the muscarinic 1 receptor cortical subtype in schizophrenia. Am J Med Genet 119B:2–6

    Article  PubMed  CAS  Google Scholar 

  • Michel MC, Parra S (2008) Similarities and differences in the autonomic control of airway and urinary bladder smooth muscle. Naunyn Schmiedebergs Arch Pharmacol 378:217–224

    Article  PubMed  CAS  Google Scholar 

  • Michel MC, Pahladsingh R, Teitsma CA et al (2009) Do M2 muscarinic receptors contribute to human bladder function in vivo? J Urol 181:570–571

    Article  Google Scholar 

  • Mishra BK, Wu T, Belfer I et al (2007) Do motor control genes contribute to interindividual variability in decreased movement in patients with pain? Mol Pain 3:20

    Article  PubMed  Google Scholar 

  • Mobascher A, Rujescu D, Mittelstraß K et al (2010) Association of a variant in the muscarinic acetylcholine receptor 2 gene (CHRM2) with nicotine addiction. Am J Med Genet B Neuropsychiatr Genet 153B:684–690

    Google Scholar 

  • Müller C, Siegmund W, Huupponen R et al (1993) Kinetics of propiverine as assessed by radioreceptor assay in poor and extensive metabolizers of debrisoquine. Eur J Drug Metab Pharmacokinet 18:265–272

    Article  PubMed  Google Scholar 

  • Ohara K, Kondo N, Xie D et al (1994) New sequences of muscarinic acetylcholine receptors (m1 and m2) in patients with Alzheimer’s disease and vascular dementia. Neurosci Lett 178:23–26

    Article  PubMed  CAS  Google Scholar 

  • Park H-W, Yang M-S, Park C-S et al (2009) Additive role of tiotropium in severe asthmatics and Arg16Gly in ADRB2 as a potential marker to predict response. Allergy 64:778–783

    Article  PubMed  CAS  Google Scholar 

  • Rosskopf D, Koch K, Habich C et al (2003) Interaction of Gβ3s, a splice wariant of the G-protein Gβ3, with Gγ- and Gα-proteins. Cell Signal 15:479–488

    Article  PubMed  CAS  Google Scholar 

  • Shi J, Hattori E, Zou H et al (2007) No evidence for association between 19 cholinergic genes and bipolar disorder. Am J Med Genet 144B:715–723

    Article  PubMed  CAS  Google Scholar 

  • Szczepankiewicz A, Breborowicz A, Sobkowiak P et al (2009) Association of A/T polymorphism of the CHRM2 gene with bronchodilator response to ipratropium bromide in asthmatic children. Pneumonol Alergol Pol 77:5–10

    PubMed  Google Scholar 

  • Wang JC, Hinrichs AL, Stock H et al (2004) Evidence of common and specific genetic effets: association of the muscarinic acetylcholine receptor M2 (CHRM2) gene with alcohol dependence and major depressive syndrome. Hum Mol Genet 13:1903–1911

    Article  PubMed  CAS  Google Scholar 

  • Weiner DM, Goodman MW, Colpitts TM et al (2004) Functional screening of drug target genes: m1 muscarinic acetylcholine receptor phenotypes in denegenerative dementias. Am J Pharmacogenomics 4:119–128

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto T, Yamashita N, Kuwabara M et al (2002) Mutation screening of the muscarinic m2 and m3 receptor genes in asthmatics, outgrouw subjects, and normal controls. Ann Genet 45:109–113

    PubMed  Google Scholar 

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Acknowledgment

Work in the authors’ lab was supported in part by Coordination Theme 1 (Health) of the European Community’s FP7, Grant agreement number HEALTH-F2-2008-223234.

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Author notes

  1. Martin C. Michel

    Present address: Boehringer Ingelheim Pharma GmbH & Co. KG, Clinical Development and Medical Affairs, HPZ 3460-05-04, Binger Straße 173, Ingelheim, 55216, Germany

Authors and Affiliations

  1. Departments of Pharmacology and Pharmacotherapy, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Martin C. Michel & Christine A. Teitsma

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  1. Martin C. Michel
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  2. Christine A. Teitsma
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Correspondence to Martin C. Michel .

Editor information

Editors and Affiliations

  1. UHN67, Department of Pulmonary and Critical Ca, Oregon Health & Science University, SW Sam Jackson Park Road 3181, Portland, 97239, Oregon, USA

    Allison D. Fryer

  2. , Department of Pharmacology, Monash Institute of Pharmaceutical Scien, Royal Parade 381, Parkville, 3052, Victoria, Australia

    Arthur Christopoulos

  3. , Department of Pharmacology, University of Washington, Seattle, 98195-7750, Washington, USA

    Neil M. Nathanson

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Michel, M.C., Teitsma, C.A. (2012). Polymorphisms in Human Muscarinic Receptor Subtype Genes. In: Fryer, A., Christopoulos, A., Nathanson, N. (eds) Muscarinic Receptors. Handbook of Experimental Pharmacology, vol 208. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-23274-9_3

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