Skip to main content
SpringerLink
Log in

Smoking-Related Genes and Functional Consequences

  • Chapter
  • First Online:
Book cover Nicotinic Receptors

Part of the book series: The Receptors ((REC,volume 26))

  • 1096 Accesses

Abstract

As the leading preventable cause of cancer and death, nicotine use and dependence have been the subject of a multitude of genetic studies in the past decade, ranging from candidate gene studies to genome-wide association studies (GWAS) to prospective studies. The genetics of nicotine addiction, smoking, and cancer are multifactorial, as would be expected from a complex behavior such as cigarette smoking. The combined heritability based on twin studies is estimated at 50–75 % (Li, Am J Med Sci 326(4): 168–73, 2003; Hall et al. Tob Control 11(2): 119–24, 2002; Lessov et al. Psychol Med 34(5): 865–79, 2004.; Lessov-Schlaggar et al. Int J Epidemiol 35(5): 1278–85, 2006; Maes et al. Psychol Med 34(7): 1251–61, 2004), with a large number of genes contributing to a small amount of risk individually. Some genes contribute to the quantity of nicotine used, while another set is associated with the duration of nicotine use, and yet another set is linked with severity of nicotine dependence. Associated “risky” genes comprise genes encoding for nicotinic acetylcholine receptor (nAChR) subunits, but also include genes like the bitter taste receptor. Still others have been associated with initiation and with success, or lack thereof, in cessation. In this chapter we review the current findings in the genetics of smoking, focusing on those studies that have linked nicotinic acetylcholine receptors (nAChR) to nicotine addiction, and further discuss how mutations in these receptors alter their function.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Lessov CN, et al. Defining nicotine dependence for genetic research: evidence from Australian twins. Psychol Med. 2004;34(5):865–79.

    PubMed  Google Scholar 

  2. Chen LS, et al. Dissection of the phenotypic and genotypic associations with nicotinic dependence. Nicotine Tob Res. 2012;14(4):425–33.

    CAS  PubMed Central  PubMed  Google Scholar 

  3. Keskitalo K, et al. Association of serum cotinine level with a cluster of three nicotinic acetylcholine receptor genes (CHRNA3/CHRNA5/CHRNB4) on chromosome 15. Hum Mol Genet. 2009;18(20):4007–12.

    CAS  PubMed Central  PubMed  Google Scholar 

  4. Rice JP, et al. CHRNB3 is more strongly associated with Fagerstrom test for cigarette dependence-based nicotine dependence than cigarettes per day: phenotype definition changes genome-wide association studies results. Addiction. 2012;107(11):2019–28.

    PubMed Central  PubMed  Google Scholar 

  5. Ware JJ, van den Bree M, Munafo MR. From men to mice: CHRNA5/CHRNA3, smoking behavior and disease. Nicotine Tob Res. 2012;14(11):1291–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Saccone SF, et al. Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs. Hum Mol Genet. 2007;16(1):36–49.

    CAS  PubMed Central  PubMed  Google Scholar 

  7. Bierut LJ, et al. Novel genes identified in a high-density genome wide association study for nicotine dependence. Hum Mol Genet. 2007;16(1):24–35.

    CAS  PubMed Central  PubMed  Google Scholar 

  8. Thorgeirsson TE, et al. A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature. 2008;452(7187):638–42.

    CAS  PubMed  Google Scholar 

  9. Hung RJ, et al. A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature. 2008;452(7187):633–7.

    CAS  PubMed  Google Scholar 

  10. Lan Q, et al. Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia. Nat Genet. 2012;44(12):1330–5.

    CAS  PubMed Central  PubMed  Google Scholar 

  11. Berrettini W, et al. Alpha-5/alpha-3 nicotinic receptor subunit alleles increase risk for heavy smoking. Mol Psychiatry. 2008;13(4):368–73.

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Chen LS, et al. Smoking and genetic risk variation across populations of European, Asian, and African American ancestry – a meta-analysis of chromosome 15q25. Genet Epidemiol. 2012;36(4):340–51.

    PubMed Central  PubMed  Google Scholar 

  13. Bierut LJ, et al. Variants in nicotinic receptors and risk for nicotine dependence. Am J Psychiatry. 2008;165(9):1163–71.

    PubMed Central  PubMed  Google Scholar 

  14. Caporaso N, et al. Genome-wide and candidate gene association study of cigarette smoking behaviors. PLoS One. 2009;4(2):e4653.

    PubMed Central  PubMed  Google Scholar 

  15. Thorgeirsson TE, et al. Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior. Nat Genet. 2010;42(5):448–53.

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Hartz SM, et al. Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers. Arch Gen Psychiatry. 2012;69(8):854–60.

    PubMed Central  PubMed  Google Scholar 

  17. Sherva R, et al. Association of a single nucleotide polymorphism in neuronal acetylcholine receptor subunit alpha 5 (CHRNA5) with smoking status and with ‘pleasurable buzz’ during early experimentation with smoking. Addiction. 2008;103(9):1544–52.

    PubMed Central  PubMed  Google Scholar 

  18. Weiss RB, et al. A candidate gene approach identifies the CHRNA5-A3-B4 region as a risk factor for age-dependent nicotine addiction. PLoS Genet. 2008;4(7):e1000125.

    PubMed Central  PubMed  Google Scholar 

  19. Stephens SH, et al. Externalizing behaviors are associated with SNPs in the CHRNA5/CHRNA3/CHRNB4 gene cluster. Behav Genet. 2012;42(3):402–14.

    PubMed Central  PubMed  Google Scholar 

  20. Chen LS, et al. Interplay of genetic risk factors (CHRNA5-CHRNA3-CHRNB4) and cessation treatments in smoking cessation success. Am J Psychiatry. 2012;169(7):735–42.

    PubMed Central  PubMed  Google Scholar 

  21. Bergen AW, et al. Nicotinic acetylcholine receptor variation and response to smoking cessation therapies. Pharmacogenet Genomics. 2013;23(2):94–103.

    CAS  PubMed Central  PubMed  Google Scholar 

  22. Freathy RM, et al. A common genetic variant in the 15q24 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) is associated with a reduced ability of women to quit smoking in pregnancy. Hum Mol Genet. 2009;18(15):2922–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  23. Heitjan DF, et al. Identification of pharmacogenetic markers in smoking cessation therapy. Am J Med Genet B Neuropsychiatr Genet. 2008;147B(6):712–9.

    PubMed Central  PubMed  Google Scholar 

  24. Conti DV, et al. Nicotinic acetylcholine receptor beta2 subunit gene implicated in a systems-based candidate gene study of smoking cessation. Hum Mol Genet. 2008;17(18):2834–48.

    CAS  PubMed Central  PubMed  Google Scholar 

  25. Sarginson JE, et al. Markers in the 15q24 nicotinic receptor subunit gene cluster (CHRNA5-A3-B4) predict severity of nicotine addiction and response to smoking cessation therapy. Am J Med Genet B Neuropsychiatr Genet. 2011;156B(3):275–84.

    PubMed  Google Scholar 

  26. Saccone NL, et al. The CHRNA5-CHRNA3-CHRNB4 nicotinic receptor subunit gene cluster affects risk for nicotine dependence in African-Americans and in European-Americans. Cancer Res. 2009;69(17):6848–56.

    CAS  PubMed Central  PubMed  Google Scholar 

  27. Liu JZ, et al. Meta-analysis and imputation refines the association of 15q25 with smoking quantity. Nat Genet. 2010;42(5):436–40.

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Tobacco and Genetics Consortium. Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nat Genet. 2010;42(5):441–7.

    Google Scholar 

  29. Harari O, et al. Pathway analysis of smoking quantity in multiple GWAS identifies cholinergic and sensory pathways. PLoS One. 2012;7(12):e50913.

    CAS  PubMed Central  PubMed  Google Scholar 

  30. Kapoor M, et al. Variants located upstream of CHRNB4 on chromosome 15q25.1 are associated with age at onset of daily smoking and habitual smoking. PLoS One. 2012;7(3):e33513.

    CAS  PubMed Central  PubMed  Google Scholar 

  31. Haller G, et al. Rare missense variants in CHRNB4 are associated with reduced risk of nicotine dependence. Hum Mol Genet. 2012;21(3):647–55.

    CAS  PubMed Central  PubMed  Google Scholar 

  32. Zeiger JS, et al. The neuronal nicotinic receptor subunit genes (CHRNA6 and CHRNB3) are associated with subjective responses to tobacco. Hum Mol Genet. 2008;17(5):724–34.

    CAS  PubMed  Google Scholar 

  33. Hoft NR, et al. Genetic association of the CHRNA6 and CHRNB3 genes with tobacco dependence in a nationally representative sample. Neuropsychopharmacology. 2009;34(3): 698–706.

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Saccone NL, et al. Multiple distinct risk loci for nicotine dependence identified by dense coverage of the complete family of nicotinic receptor subunit (CHRN) genes. Am J Med Genet B Neuropsychiatr Genet. 2009;150B(4):453–66.

    CAS  PubMed Central  PubMed  Google Scholar 

  35. Saccone NL, et al. Multiple cholinergic nicotinic receptor genes affect nicotine dependence risk in African and European Americans. Genes Brain Behav. 2010;9(7):741–50.

    CAS  PubMed Central  PubMed  Google Scholar 

  36. Bloom J, et al. The contribution of common CYP2A6 alleles to variation in nicotine metabolism among European-Americans. Pharmacogenet Genomics. 2011;21(7):403–16.

    CAS  PubMed Central  PubMed  Google Scholar 

  37. Raunio H, Rahnasto-Rilla M. CYP2A6: genetics, structure, regulation, and function. Drug Metabol Drug Interact. 2012;27(2):73–88.

    CAS  PubMed  Google Scholar 

  38. Bloom AJ, et al. Effects upon in-vivo nicotine metabolism reveal functional variation in FMO3 associated with cigarette consumption. Pharmacogenet Genomics. 2013;23(2):62–8.

    CAS  PubMed  Google Scholar 

  39. Lerman C, et al. Nicotine metabolite ratio predicts efficacy of transdermal nicotine for smoking cessation. Clin Pharmacol Ther. 2006;79(6):600–8.

    CAS  PubMed  Google Scholar 

  40. Malaiyandi V, Sellers EM, Tyndale RF. Implications of CYP2A6 genetic variation for smoking behaviors and nicotine dependence. Clin Pharmacol Ther. 2005;77(3):145–58.

    CAS  PubMed  Google Scholar 

  41. Benowitz NL. Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics. Annu Rev Pharmacol Toxicol. 2009;49:57–71.

    CAS  PubMed Central  PubMed  Google Scholar 

  42. Ray R, et al. Convergent evidence that choline acetyltransferase gene variation is associated with prospective smoking cessation and nicotine dependence. Neuropsychopharmacology. 2010;35(6):1374–82.

    CAS  PubMed Central  PubMed  Google Scholar 

  43. Wei J, et al. Replication and extension of association of choline acetyltransferase with nicotine dependence in European and African American smokers. Hum Genet. 2010;127(6): 691–8.

    CAS  PubMed  Google Scholar 

  44. Uhl GR, et al. Molecular genetics of nicotine dependence and abstinence: whole genome association using 520,000 SNPs. BMC Genet. 2007;8:10.

    PubMed Central  PubMed  Google Scholar 

  45. Vink JM, et al. Genome-wide association study of smoking initiation and current smoking. Am J Hum Genet. 2009;84(3):367–79.

    CAS  PubMed Central  PubMed  Google Scholar 

  46. Pergadia ML, et al. A 3p26-3p25 genetic linkage finding for DSM-IV major depression in heavy smoking families. Am J Psychiatry. 2011;168(8):848–52.

    PubMed Central  PubMed  Google Scholar 

  47. Yang Z, et al. Serotonin transporter and receptor genes significantly impact nicotine dependence through genetic interactions in both European American and African American smokers. Drug Alcohol Depend. 2013;129(3):217–25.

    CAS  PubMed Central  PubMed  Google Scholar 

  48. Cui WY, et al. Genetics of GABAergic signaling in nicotine and alcohol dependence. Hum Genet. 2012;131(6):843–55.

    CAS  PubMed Central  PubMed  Google Scholar 

  49. Han S, et al. Meta-analysis of 15 genome-wide linkage scans of smoking behavior. Biol Psychiatry. 2010;67(1):12–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Li MD, et al. Association and interaction analyses of GABBR1 and GABBR2 with nicotine dependence in European- and African-American populations. PLoS One. 2009;4(9):e7055.

    PubMed Central  PubMed  Google Scholar 

  51. Chen X, et al. Cannabinoid receptor 1 gene association with nicotine dependence. Arch Gen Psychiatry. 2008;65(7):816–24.

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Le Merrer J, et al. Reward processing by the opioid system in the brain. Physiol Rev. 2009;89(4):1379–412.

    PubMed  Google Scholar 

  53. Liu X, Jernigan C. Activation of the opioid mu1, but not delta or kappa, receptors is required for nicotine reinforcement in a rat model of drug self-administration. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(1):146–53.

    CAS  PubMed Central  PubMed  Google Scholar 

  54. Zhang L, Kendler KS, Chen X. The mu-opioid receptor gene and smoking initiation and nicotine dependence. Behav Brain Funct. 2006;2:28.

    PubMed Central  PubMed  Google Scholar 

  55. Verhagen M, Kleinjan M, Engels RC. A systematic review of the A118G (Asn40Asp) variant of OPRM1 in relation to smoking initiation, nicotine dependence and smoking cessation. Pharmacogenomics. 2012;13(8):917–33.

    CAS  PubMed  Google Scholar 

  56. Chen YT, et al. OPRM1 genetic polymorphisms are associated with the plasma nicotine metabolite cotinine concentration in methadone maintenance patients: a cross sectional study. J Hum Genet. 2013;58(2):84–90.

    CAS  PubMed  Google Scholar 

  57. Domino EF, et al. Tobacco smoking produces greater striatal dopamine release in G-allele carriers with mu opioid receptor A118G polymorphism. Prog Neuropsychopharmacol Biol Psychiatry. 2012;38(2):236–40.

    CAS  PubMed  Google Scholar 

  58. Ray R, et al. Human Mu Opioid Receptor (OPRM1 A118G) polymorphism is associated with brain mu-opioid receptor binding potential in smokers. Proc Natl Acad Sci U S A. 2011;108(22):9268–73.

    CAS  PubMed Central  PubMed  Google Scholar 

  59. Hardin J, et al. Nicotine withdrawal sensitivity, linkage to chr6q26, and association of OPRM1 SNPs in the SMOking in FAMilies (SMOFAM) sample. Cancer Epidemiol Biomarkers Prev. 2009;18(12):3399–406.

    CAS  PubMed Central  PubMed  Google Scholar 

  60. Ray R, et al. Association of OPRM1 A118G variant with the relative reinforcing value of nicotine. Psychopharmacology (Berl). 2006;188(3):355–63.

    CAS  Google Scholar 

  61. Munafo MR, et al. Association of the DRD2 gene Taq1A polymorphism and smoking behavior: a meta-analysis and new data. Nicotine Tob Res. 2009;11(1):64–76.

    CAS  PubMed Central  PubMed  Google Scholar 

  62. Johnstone EC, et al. Genetic variation in dopaminergic pathways and short-term effectiveness of the nicotine patch. Pharmacogenetics. 2004;14(2):83–90.

    CAS  PubMed  Google Scholar 

  63. Lerman C, et al. Role of functional genetic variation in the dopamine D2 receptor (DRD2) in response to bupropion and nicotine replacement therapy for tobacco dependence: results of two randomized clinical trials. Neuropsychopharmacology. 2006;31(1):231–42.

    CAS  PubMed  Google Scholar 

  64. Yudkin P, et al. Effectiveness of nicotine patches in relation to genotype in women versus men: randomised controlled trial. BMJ. 2004;328(7446):989–90.

    PubMed Central  PubMed  Google Scholar 

  65. David SP, et al. Bupropion efficacy for smoking cessation is influenced by the DRD2 Taq1A polymorphism: analysis of pooled data from two clinical trials. Nicotine Tob Res. 2007;9(12): 1251–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  66. Swan GE, et al. Dopamine receptor DRD2 genotype and smoking cessation outcome following treatment with bupropion SR. Pharmacogenomics J. 2005;5(1):21–9.

    CAS  PubMed  Google Scholar 

  67. Jackson KJ, et al. The neuropeptide galanin and variants in the GalR1 gene are associated with nicotine dependence. Neuropsychopharmacology. 2011;36(11):2339–48.

    CAS  PubMed Central  PubMed  Google Scholar 

  68. Lori A, et al. The galanin receptor 1 gene associates with tobacco craving in smokers seeking cessation treatment. Neuropsychopharmacology. 2011;36(7):1412–20.

    CAS  PubMed Central  PubMed  Google Scholar 

  69. Lerman C, et al. Individualizing nicotine replacement therapy for the treatment of tobacco dependence: a randomized trial. Ann Intern Med. 2004;140(6):426–33.

    CAS  PubMed  Google Scholar 

  70. Schnoll RA, et al. Effectiveness of extended-duration transdermal nicotine therapy: a randomized trial. Ann Intern Med. 2010;152(3):144–51.

    PubMed Central  PubMed  Google Scholar 

  71. Gold AB, et al. Pharmacogenetic association of the galanin receptor (GALR1) SNP rs2717162 with smoking cessation. Neuropsychopharmacology. 2012;37(7):1683–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  72. Bierut LJ. Genetic vulnerability and susceptibility to substance dependence. Neuron. 2011;69(4):618–27.

    CAS  PubMed Central  PubMed  Google Scholar 

  73. Corringer PJ, Sallette J, Changeux JP. Nicotine enhances intracellular nicotinic receptor maturation: a novel mechanism of neural plasticity? J Physiol Paris. 2006;99(2–3):162–71.

    CAS  PubMed  Google Scholar 

  74. Falvella FS, et al. Transcription deregulation at the 15q25 locus in association with lung adenocarcinoma risk. Clin Cancer Res. 2009;15(5):1837–42.

    CAS  PubMed  Google Scholar 

  75. Saccone NL, et al. Multiple independent loci at chromosome 15q25.1 affect smoking quantity: a meta-analysis and comparison with lung cancer and COPD. PLoS Genet. 2010;6(8): e1001053.

    PubMed Central  PubMed  Google Scholar 

  76. Smith RM, et al. Nicotinic alpha5 receptor subunit mRNA expression is associated with distant 5′ upstream polymorphisms. Eur J Hum Genet. 2011;19(1):76–83.

    CAS  PubMed Central  PubMed  Google Scholar 

  77. Wang JC, et al. Risk for nicotine dependence and lung cancer is conferred by mRNA expression levels and amino acid change in CHRNA5. Hum Mol Genet. 2009;18(16):3125–35.

    CAS  PubMed Central  PubMed  Google Scholar 

  78. Frahm S, et al. Aversion to nicotine is regulated by the balanced activity of beta4 and alpha5 nicotinic receptor subunits in the medial habenula. Neuron. 2011;70(3):522–35.

    CAS  PubMed  Google Scholar 

  79. Ebihara M, et al. Genomic organization and promoter analysis of the human nicotinic acetylcholine receptor alpha6 subunit (CHNRA6) gene: Alu and other elements direct transcriptional repression. Gene. 2002;298(1):101–8.

    CAS  PubMed  Google Scholar 

  80. Improgo MR, et al. The nicotinic acetylcholine receptor CHRNA5/A3/B4 gene cluster: dual role in nicotine addiction and lung cancer. Prog Neurobiol. 2010;92(2):212–26.

    CAS  PubMed Central  PubMed  Google Scholar 

  81. Boulter J, et al. Alpha 3, alpha 5, and beta 4: three members of the rat neuronal nicotinic acetylcholine receptor-related gene family form a gene cluster. J Biol Chem. 1990;265(8): 4472–82.

    CAS  PubMed  Google Scholar 

  82. Pugh BF, Tjian R. Transcription from a TATA-less promoter requires a multisubunit TFIID complex. Genes Dev. 1991;5(11):1935–45.

    CAS  PubMed  Google Scholar 

  83. Xu X, Scott MM, Deneris ES. Shared long-range regulatory elements coordinate expression of a gene cluster encoding nicotinic receptor heteromeric subtypes. Mol Cell Biol. 2006;26(15):5636–49.

    CAS  PubMed Central  PubMed  Google Scholar 

  84. Flora AV, et al. Functional characterization of SNPs in CHRNA3/B4 intergenic region associated with drug behaviors. Brain Res. 2013;1529:1–15.

    CAS  PubMed  Google Scholar 

  85. Solda G, et al. In vivo RNA-RNA duplexes from human alpha3 and alpha5 nicotinic receptor subunit mRNAs. Gene. 2005;345(2):155–64.

    CAS  PubMed  Google Scholar 

  86. Gallego X, et al. Alternative CHRNB4 3′-UTRs mediate the allelic effects of SNP rs1948 on gene expression. PLoS One. 2013;8(5):e63699.

    CAS  PubMed Central  PubMed  Google Scholar 

  87. Eggert M, et al. Nicotinic acetylcholine receptor subunits alpha4 and alpha5 associated with smoking behaviour and lung cancer are regulated by upstream open reading frames. PLoS One. 2013;8(7):e66157.

    CAS  PubMed Central  PubMed  Google Scholar 

  88. Kuryatov A, Berrettini W, Lindstrom J. Acetylcholine receptor (AChR) alpha5 subunit variant associated with risk for nicotine dependence and lung cancer reduces (alpha4beta2)(2)alpha5 AChR function. Mol Pharmacol. 2011;79(1):119–25.

    CAS  PubMed Central  PubMed  Google Scholar 

  89. Li P, et al. Functional characterization of the alpha5(Asn398) variant associated with risk for nicotine dependence in the alpha3beta4alpha5 nicotinic receptor. Mol Pharmacol. 2011; 80(5):818–27.

    CAS  PubMed Central  PubMed  Google Scholar 

  90. Tammimaki A, et al. Impact of human D398N single nucleotide polymorphism on intracellular calcium response mediated by alpha3beta4alpha5 nicotinic acetylcholine receptors. Neuropharmacology. 2012;63(6):1002–11.

    CAS  PubMed Central  PubMed  Google Scholar 

  91. Peters JA, et al. Novel structural determinants of single channel conductance and ion selectivity in 5-hydroxytryptamine type 3 and nicotinic acetylcholine receptors. J Physiol. 2010; 588(Pt 4):587–96.

    CAS  PubMed Central  PubMed  Google Scholar 

  92. Carland JE, et al. Characterization of the effects of charged residues in the intracellular loop on ion permeation in alpha1 glycine receptor channels. J Biol Chem. 2009;284(4):2023–30.

    CAS  PubMed  Google Scholar 

  93. Kelley SP, et al. A cytoplasmic region determines single-channel conductance in 5-HT3 receptors. Nature. 2003;424(6946):321–4.

    CAS  PubMed  Google Scholar 

  94. Bond C, et al. Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction. Proc Natl Acad Sci U S A. 1998;95(16):9608–13.

    CAS  PubMed Central  PubMed  Google Scholar 

  95. Beyer A, et al. Effect of the A118G polymorphism on binding affinity, potency and agonist-mediated endocytosis, desensitization, and resensitization of the human mu-opioid receptor. J Neurochem. 2004;89(3):553–60.

    CAS  PubMed  Google Scholar 

  96. Zhang Y, et al. Allelic expression imbalance of human mu opioid receptor (OPRM1) caused by variant A118G. J Biol Chem. 2005;280(38):32618–24.

    CAS  PubMed  Google Scholar 

  97. Mague SD, et al. Mouse model of OPRM1 (A118G) polymorphism has sex-specific effects on drug-mediated behavior. Proc Natl Acad Sci U S A. 2009;106(26):10847–52.

    CAS  PubMed Central  PubMed  Google Scholar 

  98. Changeux JP. Nicotine addiction and nicotinic receptors: lessons from genetically modified mice. Nat Rev Neurosci. 2010;11(6):389–401.

    CAS  PubMed  Google Scholar 

  99. Fowler CD, et al. Habenular alpha5 nicotinic receptor subunit signalling controls nicotine intake. Nature. 2011;471(7340):597–601.

    CAS  PubMed Central  PubMed  Google Scholar 

  100. Salas R, et al. Nicotinic receptors in the habenulo-interpeduncular system are necessary for nicotine withdrawal in mice. J Neurosci. 2009;29(10):3014–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  101. Gallego X, et al. Overexpression of the CHRNA5/A3/B4 genomic cluster in mice increases the sensitivity to nicotine and modifies its reinforcing effects. Amino Acids. 2012;43(2):897–909.

    CAS  PubMed  Google Scholar 

  102. Exley R, et al. Striatal alpha5 nicotinic receptor subunit regulates dopamine transmission in dorsal striatum. J Neurosci. 2012;32(7):2352–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  103. Tolu S, et al. Co-activation of VTA DA and GABA neurons mediates nicotine reinforcement. Mol Psychiatry. 2013;18(3):382–93.

    CAS  PubMed  Google Scholar 

  104. Chatterjee S, et al. The alpha5 subunit regulates the expression and function of alpha4*-containing neuronal nicotinic acetylcholine receptors in the ventral-tegmental area. PLoS One. 2013;8(7):e68300.

    CAS  PubMed Central  PubMed  Google Scholar 

  105. Zalud AW, Helfand RS, Tammimaki AE, Nguyen V, Stitzel JA. The nicotinic receptor α5 subunit polymorphism (CHRNA5 D398N) increases nicotine consumption and mitigates withdrawal-related disruptions in mesolimbic neurochemistry. 2012. 532.11/B38.

    Google Scholar 

  106. Hong LE, et al. A genetically modulated, intrinsic cingulate circuit supports human nicotine addiction. Proc Natl Acad Sci U S A. 2010;107(30):13509–14.

    CAS  PubMed Central  PubMed  Google Scholar 

  107. Lessov-Schlaggar CN, et al. Heritability of cigarette smoking and alcohol use in Chinese male twins: the Qingdao twin registry. Int J Epidemiol. 2006;35(5):1278–85.

    PubMed  Google Scholar 

  108. Li MD. The genetics of smoking related behavior: a brief review. Am J Med Sci. 2003;326(4): 168–73.

    PubMed  Google Scholar 

  109. Hall W, Madden P, Lynskey M. The genetics of tobacco use: methods, findings and policy implications. Tob Control. 2002;11(2):119–24.

    CAS  PubMed Central  PubMed  Google Scholar 

  110. Maes HH, et al. A twin study of genetic and environmental influences on tobacco initiation, regular tobacco use and nicotine dependence. Psychol Med. 2004;34(7):1251–61.

    PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Samin Shehab for his invaluable assistance in assembling the reference material in Table 17.1.

Author information

Authors and Affiliations

  1. Laboratory of Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA

    Ines Ibañez-Tallon Ph.D. & Jessica L. Ables M.D., Ph.D.

Authors
  1. Ines Ibañez-Tallon Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jessica L. Ables M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ines Ibañez-Tallon Ph.D. .

Editor information

Editors and Affiliations

  1. Department of Neurobiology SHEL 1006, University of Alabama at Birmingham, Birmingham, Alabama, USA

    Robin A.J. Lester

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Ibañez-Tallon, I., Ables, J.L. (2014). Smoking-Related Genes and Functional Consequences. In: Lester, R. (eds) Nicotinic Receptors. The Receptors, vol 26. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1167-7_17

Download citation

Publish with us

Policies and ethics

Search

Navigation