Skip to main content

Advertisement

SpringerLink
Log in

Nicotinic acetylcholine gene cluster CHRNA5-A3-B4 variants influence smoking status in a Bangladeshi population

  • Article
  • Published:
Pharmacological Reports Aims and scope Submit manuscript

Abstract

Background

Past studies have established the association of CHRNA5-A3-B4 gene cluster variants with various smoking behaviors in different ethnicities, yet no such study has been reported in Bengali ethnicity to date.

Methods

A case–control study with 129 smokers and 111 non-smokers was conducted and genotyped using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method aimed to manifest the association of three SNPs in this gene cluster with smoking status (SS) in a Bangladeshi population.

Results

The non-synonymous CHRNA5 rs1s6969968 and 3′-UTR variant CHRNA3 rs578776 polymorphisms were found to have a strong association with SS. Carriers of polymorphic ‘A’ allele of rs16969968 showed 1.51-fold more risk of being smokers (adjusted OR = 1.51, 95% CI 0.88–2.57, p = 0.128); whereas, rs578776 polymorphic ‘A’ allele carriers showed 0.595-fold less risk of being smokers (adjusted OR = 1.51, 95% CI 0.88–2.57, p = 0.006). Comparing smokers and non-smokers, A/A mutant homozygous genotypes of rs578776 and rs16969968 variants pose 0.369-fold (95% CI 0.177–0.77, p = 0.008) and 3.3-fold (95% CI 0.66–16.46, p = 0.14) more risk for positive SS, respectively. No genotypic association for SS was found with intronic variant CHRNB4 rs11072768 (T/G; adjusted OR = 0.827, 95% CI 0.457–1.499, p = 0.532 and G/G; adjusted OR = 0.992, 95% CI 0.455–2.167, p = 0.985). Combination of rs16969968-positive/rs578776-negative polymorphic variants possesses the risk of positive SS in young adults. Furthermore, two new haplotypes (AAT and AAG) were identified in Bangladeshi population and GAG (OR = 0.45, 95% CI 0.25–0.8, p = 0.006) haplotype was found to be a protective factor for SS.

Conclusion

Nicotinic acetylcholine gene cluster CHRNA5-A3-B4 variants rs16969968 and rs578776 are associated with SS in a Bangladeshi population. Large-scale studies are warranted to establish this genotype–phenotype correlation.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Data availability

All data generated or analyzed during this study are included in this published article.

References

  1. WHO EMRO. Number of males using tobacco globally on the decline, showing that government-led control efforts work to save lives, protect health, beat tobacco | News | Media centre n.d. http://www.emro.who.int/media/news/number-of-males-using-tobacco-globally-on-the-decline-showing-that-government-led-control-efforts-work-to-save-lives-protect-health-beat-tobacco.html (Accessed July 3, 2020).

  2. Hasan M. WHO: tobacco responsible for 1 in 5 deaths in Bangladesh. Dhaka Tribune 2018. https://www.dhakatribune.com/health/2018/06/01/tobacco-1-in-5-deaths-bangladesh (Accessed July 3, 2020).

  3. Faruque G, Wadood S, Ahmed M, Parven R, Huq I, Chowdhury S (2019). The economic cost of tobacco use in Bangladesh: a health cost approach. Bangladesh Cancer SOciety.

  4. Edwards KL, Austin MA, Jarvik GP. Evidence for genetic influences on smoking in adult women twins. Clin Genet. 1995;47:236–44. https://doi.org/10.1111/j.1399-0004.1995.tb04303.x.

    Article  CAS  PubMed  Google Scholar 

  5. Facchini FS, Hollenbeck CB, Jeppesen J, Chen YD, Reaven GM. Insulin resistance and cigarette smoking. Lancet. 1992;339:1128–30. https://doi.org/10.1016/0140-6736(92)90730-q.

    Article  CAS  PubMed  Google Scholar 

  6. Hughes JR, Stead LF, Lancaster T. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2007. https://doi.org/10.1002/14651858.CD000031.pub3.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2004. https://doi.org/10.1002/14651858.CD000146.pub2.

    Article  PubMed  Google Scholar 

  8. Fowler T, Lifford K, Shelton K, Rice F, Thapar A, Neale MC, et al. Exploring the relationship between genetic and environmental influences on initiation and progression of substance use. Addiction. 2007;102:413–22. https://doi.org/10.1111/j.1360-0443.2006.01694.x.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Lessov CN, Martin NG, Statham DJ, Todorov AA, Slutske WS, Bucholz KK, et al. Defining nicotine dependence for genetic research: evidence from Australian twins. Psychol Med. 2004;34:865–79. https://doi.org/10.1017/s0033291703001582.

    Article  PubMed  Google Scholar 

  10. Munafò MR, Johnstone EC. Genes and cigarette smoking. Addiction. 2008;103:893–904. https://doi.org/10.1111/j.1360-0443.2007.02071.x.

    Article  PubMed  Google Scholar 

  11. Arinami T, Ishiguro H, Onaivi ES. Polymorphisms in genes involved in neurotransmission in relation to smoking. Eur J Pharmacol. 2000;410:215–26. https://doi.org/10.1016/s0014-2999(00)00816-5.

    Article  CAS  PubMed  Google Scholar 

  12. Carmelli D, Swan GE, Robinette D, Fabsitz R. Genetic influence on smoking–a study of male twins. N Engl J Med. 1992;327:829–33. https://doi.org/10.1056/NEJM199209173271201.

    Article  CAS  PubMed  Google Scholar 

  13. True WR, Heath AC, Scherrer JF, Waterman B, Goldberg J, Lin N, et al. Genetic and environmental contributions to smoking. Addiction. 1997;92:1277–87.

    Article  CAS  Google Scholar 

  14. Heath AC, Kirk KM, Meyer JM, Martin NG. Genetic and social determinants of initiation and age at onset of smoking in Australian twins. Behav Genet. 1999;29:395–407. https://doi.org/10.1023/A:1021670703806.

    Article  CAS  PubMed  Google Scholar 

  15. Kendler KS, Neale MC, Sullivan P, Corey LA, Gardner CO, Prescott CA. A population-based twin study in women of smoking initiation and nicotine dependence. Psychol Med. 1999;29:299–308. https://doi.org/10.1017/s0033291798008022.

    Article  CAS  PubMed  Google Scholar 

  16. Madden PAF, Heath AC, Pedersen NL, Kaprio J, Koskenvuo MJ, Martin NG. The genetics of smoking persistence in men and women: a multicultural study. Behav Genet. 1999;29:423–31. https://doi.org/10.1023/A:1021674804714.

    Article  CAS  PubMed  Google Scholar 

  17. Sullivan PF, Kendler KS. The genetic epidemiology of smoking. Nicotine Tob Res. 1999. https://doi.org/10.1080/14622299050011811 (1 Suppl 2:S51-57; discussion S69-70).

    Article  PubMed  Google Scholar 

  18. Brunzell DH, Stafford AM, Dixon CI. Nicotinic receptor contributions to smoking: insights from human studies and animal models. Curr Addict Rep. 2015;2:33–46. https://doi.org/10.1007/s40429-015-0042-2.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Cosgrove KP, Esterlis I, Sandiego C, Petrulli R, Morris ED. Imaging tobacco smoking with PET and SPECT. Curr Top Behav Neurosci. 2015;24:1–17. https://doi.org/10.1007/978-3-319-13482-6_1.

    Article  CAS  PubMed  Google Scholar 

  20. Dani JA. Chapter one: neuronal nicotinic acetylcholine receptor structure and function and response to nicotine. In: De Biasi M, editor. International review of neurobiology, vol. 124. United States: Academic press; 2015. p. 3–19.

    Google Scholar 

  21. Liu JZ, Tozzi F, Waterworth DM, Pillai SG, Muglia P, Middleton L, et al. Meta-analysis and imputation refines the association of 15q25 with smoking quantity. Nat Genet. 2010;42:436–40. https://doi.org/10.1038/ng.572.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Mohamed TS, Jayakar SS, Hamouda AK. Orthosteric and allosteric ligands of nicotinic acetylcholine receptors for smoking cessation. Front Mol Neurosci. 2015;8:71. https://doi.org/10.3389/fnmol.2015.00071.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Thorgeirsson TE, Gudbjartsson DF, Surakka I, Vink JM, Amin N, Geller F, et al. Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior. Nat Genet. 2010;42:448–53. https://doi.org/10.1038/ng.573.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Tobacco and Genetics Consortium. Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nat Genet. 2010;42:441–7. https://doi.org/10.1038/ng.571.

    Article  CAS  Google Scholar 

  25. Wang Q, Li S, Pan L, Li H, Yang X, Jiang F, et al. Association between variants in nicotinic acetylcholine receptor genes and smoking cessation in a Chinese rural population. Am J Addict. 2016;25:297–300. https://doi.org/10.1111/ajad.12383.

    Article  PubMed  Google Scholar 

  26. Perry DC, Dávila-García MI, Stockmeier CA, Kellar KJ. Increased nicotinic receptors in brains from smokers: membrane binding and autoradiography studies. J Pharmacol Exp Ther. 1999;289:1545–52.

    CAS  PubMed  Google Scholar 

  27. Csordas A, Bernhard D. The biology behind the atherothrombotic effects of cigarette smoke. Nat Rev Cardiol. 2013;10:219–30. https://doi.org/10.1038/nrcardio.2013.8.

    Article  CAS  PubMed  Google Scholar 

  28. Wen L, Jiang K, Yuan W, Cui W, Li MD. Contribution of variants in CHRNA5/A3/B4 gene cluster on chromosome 15 to tobacco smoking: from genetic association to mechanism. Mol Neurobiol. 2016;53:472–84. https://doi.org/10.1007/s12035-014-8997-x.

    Article  CAS  PubMed  Google Scholar 

  29. Gotti C, MichaelJ M, Millar NS, Wonnacott S. Nicotinic acetylcholine receptors (version 2019.4) in the IUPHAR/BPS guide to pharmacology database. GtoPdb CITE. 2019. https://doi.org/10.2218/gtopdb/F76/2019.4.

    Article  Google Scholar 

  30. Lindstrom JM. Nicotinic acetylcholine receptors of muscles and nerves. Ann NY Acad Sci. 2003;998:41–52. https://doi.org/10.1196/annals.1254.007.

    Article  CAS  PubMed  Google Scholar 

  31. Amos CI, Wu X, Broderick P, Gorlov IP, Gu J, Eisen T, et al. Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Genet. 2008;40:616–22. https://doi.org/10.1038/ng.109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Jensen KP, DeVito EE, Herman AI, Valentine GW, Gelernter J, Sofuoglu M. A CHRNA5 smoking risk variant decreases the aversive effects of nicotine in humans. Neuropsychopharmacology. 2015;40:2813–21. https://doi.org/10.1038/npp.2015.131.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Pintarelli G, Galvan A, Pozzi P, Noci S, Pasetti G, Sala F, et al. Pharmacogenetic study of seven polymorphisms in three nicotinic acetylcholine receptor subunits in smoking-cessation therapies. Sci Rep. 2017;7:16730. https://doi.org/10.1038/s41598-017-16946-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Thorgeirsson TE, Geller F, Sulem P, Rafnar T, Wiste A, Magnusson KP, et al. A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature. 2008;452:638–42. https://doi.org/10.1038/nature06846.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Bierut LJ, Stitzel JA, Wang JC, Hinrichs AL, Grucza RA, Xuei X, et al. Variants in nicotinic receptors and risk for nicotine dependence. Am J Psychiatry. 2008;165:1163–71. https://doi.org/10.1176/appi.ajp.2008.07111711.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Hong LE, Yang X, Wonodi I, Hodgkinson CA, Goldman D, Stine OC, et al. A CHRNA5 allele related to nicotine addiction and schizophrenia. Genes Brain Behav. 2011;10:530–5. https://doi.org/10.1111/j.1601-183X.2011.00689.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Sherva R, Wilhelmsen K, Pomerleau CS, Chasse SA, Rice JP, Snedecor SM, 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;103:1544–52. https://doi.org/10.1111/j.1360-0443.2008.02279.x.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Kendler KS, Chen X, Dick D, Maes H, Gillespie N, Neale MC, et al. Recent advances in the genetic epidemiology and molecular genetics of substance use disorders. Nat Neurosci. 2012;15:181–9. https://doi.org/10.1038/nn.3018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Saccone NL, Wang JC, Breslau N, Johnson EO, Hatsukami D, Saccone SF, 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;69:6848–56. https://doi.org/10.1158/0008-5472.CAN-09-0786.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhu AZX, Renner CC, Hatsukami DK, Benowitz NL, Tyndale RF. CHRNA5-A3-B4 genetic variants alter nicotine intake and interact with tobacco use to influence body weight in Alaska Native tobacco users. Addiction. 2013;108:1818–28. https://doi.org/10.1111/add.12250.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Baker TB, Weiss RB, Bolt D, von Niederhausern A, Fiore MC, Dunn DM, et al. Human neuronal acetylcholine receptor A5–A3-B4 haplotypes are associated with multiple nicotine dependence phenotypes. Nicotine Tob Res. 2009;11:785–96. https://doi.org/10.1093/ntr/ntp064.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Hamidovic A, Kasberger JL, Young TR, Goodloe RJ, Redline S, Buxbaum SG, et al. Genetic variability of smoking persistence in African Americans. Cancer Prev Res (Phila). 2011;4:729–34. https://doi.org/10.1158/1940-6207.CAPR-10-0362.

    Article  CAS  Google Scholar 

  43. Li MD, Yoon D, Lee J-Y, Han B-G, Niu T, Payne TJ, et al. Associations of variants in CHRNA5/A3/B4 gene cluster with smoking behaviors in a Korean population. PLoS ONE. 2010;5:e12183. https://doi.org/10.1371/journal.pone.0012183.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Zhang Y, Jiang M, Li Q, Liang W, He Q, Chen W, et al. Chromosome 15q25 (CHRNA3-CHRNB4) variation indirectly impacts lung cancer risk in Chinese males. PLoS ONE. 2016;11:e0149946. https://doi.org/10.1371/journal.pone.0149946.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Weiss RB, Baker TB, Cannon DS, von Niederhausern A, Dunn DM, Matsunami N, 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:e1000125. https://doi.org/10.1371/journal.pgen.1000125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. World Health Organization, editor (1998). Guidelines for controlling and monitoring the tobacco epidemic. Geneva: World Health Organization.

  47. World medical association Declaration of Helsinki. Ethical principles for medical research involving human subjects. JAMA. 2013;310:2191–4. https://doi.org/10.1001/jama.2013.281053.

    Article  CAS  Google Scholar 

  48. Bin Sayeed MS, Hasan Apu MN, Munir MT, Ahmed MU, Islam MS, Haq MM, et al. Prevalence of CYP2C19 alleles, pharmacokinetic and pharmacodynamic variation of clopidogrel and prasugrel in Bangladeshi population. Clin Exp Pharmacol Physiol. 2015;42:451–7. https://doi.org/10.1111/1440-1681.12390.

    Article  CAS  PubMed  Google Scholar 

  49. Auton A, Abecasis GR, Altshuler DM, Durbin RM, Abecasis GR, Bentley DR, et al. A global reference for human genetic variation. Nature. 2015;526:68–74. https://doi.org/10.1038/nature15393.

    Article  CAS  PubMed  Google Scholar 

  50. Freathy RM, Ring SM, Shields B, Galobardes B, Knight B, Weedon MN, 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;18:2922–7. https://doi.org/10.1093/hmg/ddp216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Grucza RA, Johnson EO, Krueger RF, Breslau N, Saccone NL, Chen L-S, et al. Incorporating age at onset of smoking into genetic models for nicotine dependence: evidence for interaction with multiple genes. Addict Biol. 2010;15:346–57. https://doi.org/10.1111/j.1369-1600.2010.00220.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Lassi G, Tan V, Mahedy L, Oliveira ASF, Dyer ML, Drax K, et al. Exploration of the role of CHRNA5-A3-B4 genotype in smoking behaviours. BioRxiv. 2019. https://doi.org/10.1101/818252.

    Article  Google Scholar 

  53. Li MD. Involvement of Variants in gene clusters CHRNA5/A3/B4 on chromosome 15 to smoking behaviors and lung cancer. In: Li MD, editor. Tobacco smoking addiction: epidemiology, genetics, mechanisms, and treatment. Singapore: Springer; 2018. p. 47–69.

    Google Scholar 

  54. Sarginson JE, Killen JD, Lazzeroni LC, Fortmann SP, Ryan HS, Schatzberg AF, 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:275–84. https://doi.org/10.1002/ajmg.b.31155.

    Article  PubMed  Google Scholar 

  55. Schlaepfer IR, Hoft NR, Collins AC, Corley RP, Hewitt JK, Hopfer CJ, et al. The CHRNA5/A3/B4 gene cluster variability as an important determinant of early alcohol and tobacco initiation in young adults. Biol Psychiatry. 2008;63:1039–46. https://doi.org/10.1016/j.biopsych.2007.10.024.

    Article  CAS  PubMed  Google Scholar 

  56. Sorice R, Bione S, Sansanelli S, Ulivi S, Athanasakis E, Lanzara C, et al. Association of a variant in the CHRNA5-A3-B4 gene cluster region to heavy smoking in the Italian population. Eur J Hum Genet. 2011;19:593–6. https://doi.org/10.1038/ejhg.2010.240.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Adjangba C, Border R, Villela PNR, Ehringer MA, Evans LM. Little evidence of modified genetic effect of rs16969968 on heavy smoking based on age of onset of smoking. MedRxiv. 2020. https://doi.org/10.1101/2020.04.22.20071407 (2020.04.22.20071407).

    Article  Google Scholar 

  58. Berrettini W, Yuan X, Tozzi F, Song K, Francks C, Chilcoat H, et al. Alpha-5/alpha-3 nicotinic receptor subunit alleles increase risk for heavy smoking. Mol Psychiatry. 2008;13:368–73. https://doi.org/10.1038/sj.mp.4002154.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Caporaso N, Gu F, Chatterjee N, Sheng-Chih J, Yu K, Yeager M, et al. Genome-wide and candidate gene association study of cigarette smoking behaviors. PLoS ONE. 2009;4:e4653. https://doi.org/10.1371/journal.pone.0004653.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Leung T, Bergen A, Munafò MR, De Ruyck K, Selby P, De Luca V. Effect of the rs1051730–rs16969968 variant and smoking cessation treatment: a meta-analysis. Pharmacogenomics. 2015;16:713–20. https://doi.org/10.2217/pgs.15.34.

    Article  CAS  PubMed  Google Scholar 

  61. Lips EH, Gaborieau V, McKay JD, Chabrier A, Hung RJ, Boffetta P, et al. Association between a 15q25 gene variant, smoking quantity and tobacco-related cancers among 17 000 individuals. Int J Epidemiol. 2010;39:563–77. https://doi.org/10.1093/ije/dyp288.

    Article  PubMed  Google Scholar 

  62. Macqueen DA, Heckman BW, Blank MD, Janse Van Rensburg K, Park JY, Drobes DJ, et al. Variation in the α 5 nicotinic acetylcholine receptor subunit gene predicts cigarette smoking intensity as a function of nicotine content. Pharmacogenomics J. 2014;14:70–6. https://doi.org/10.1038/tpj.2012.50.

    Article  CAS  PubMed  Google Scholar 

  63. Pandey N, Pal S, Sharma LK, Guleria R, Mohan A, Srivastava T. SNP rs16969968 as a strong predictor of nicotine dependence and lung cancer risk in a north indian population. Asian Pac J Cancer Prev. 2017;18:3073–9. https://doi.org/10.22034/APJCP.2017.18.11.3073.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Pérez-Morales R, González-Zamora A, González-Delgado MF, Rincón EYC, Calderón EHO, Martínez-Ramírez OC, et al. CHRNA3 rs1051730 and CHRNA5 rs16969968 polymorphisms are associated with heavy smoking, lung cancer, and chronic obstructive pulmonary disease in a mexican population. Ann Hum Genet. 2018;82:415–24. https://doi.org/10.1111/ahg.12264.

    Article  CAS  PubMed  Google Scholar 

  65. Ramirez-Latorre J, Yu CR, Qu X, Perin F, Karlin A, Role L. Functional contributions of alpha5 subunit to neuronal acetylcholine receptor channels. Nature. 1996;380:347–51. https://doi.org/10.1038/380347a0.

    Article  CAS  PubMed  Google Scholar 

  66. Sciaccaluga M, Moriconi C, Martinello K, Catalano M, Bermudez I, Stitzel JA, et al. Crucial role of nicotinic α5 subunit variants for Ca2+ fluxes in ventral midbrain neurons. FASEB J. 2015;29:3389–98. https://doi.org/10.1096/fj.14-268102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Stevens VL, Bierut LJ, Talbot JT, Wang JC, Sun J, Hinrichs AL, et al. Nicotinic receptor gene variants influence susceptibility to heavy smoking. Cancer Epidemiol Biomarkers Prev. 2008;17:3517–25. https://doi.org/10.1158/1055-9965.EPI-08-0585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Tapia L, Kuryatov A, Lindstrom J. Ca2+ permeability of the (alpha4)3(beta2)2 stoichiometry greatly exceeds that of (alpha4)2(beta2)3 human acetylcholine receptors. Mol Pharmacol. 2007;71:769–76. https://doi.org/10.1124/mol.106.030445.

    Article  CAS  PubMed  Google Scholar 

  69. Nees F, Witt SH, Lourdusamy A, Vollstädt-Klein S, Steiner S, Poustka L, et al. Genetic risk for nicotine dependence in the cholinergic system and activation of the brain reward system in healthy adolescents. Neuropsychopharmacology. 2013;38:2081–9. https://doi.org/10.1038/npp.2013.131.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Saccone SF, Hinrichs AL, Saccone NL, Chase GA, Konvicka K, Madden PAF, et al. Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs. Hum Mol Genet. 2007;16:36–49. https://doi.org/10.1093/hmg/ddl438.

    Article  CAS  PubMed  Google Scholar 

  71. Saccone NL, Culverhouse RC, Schwantes-An T-H, Cannon DS, Chen X, Cichon S, 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. https://doi.org/10.1371/journal.pgen.1001053.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Saccone NL, Saccone SF, Hinrichs AL, Stitzel JA, Duan W, Pergadia ML, 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:453–66. https://doi.org/10.1002/ajmg.b.30828.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Gold AB, Lerman C. Pharmacogenetics of smoking cessation: role of nicotine target and metabolism genes. Hum Genet. 2012. https://doi.org/10.1007/s00439-012-1143-9.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Kuryatov A, Berrettini W, Lindstrom J. Acetylcholine receptor (AChR) α5 subunit variant associated with risk for nicotine dependence and lung cancer reduces (α4β2)2α5 AChR function. Mol Pharmacol. 2011;79:119–25. https://doi.org/10.1124/mol.110.066357.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Hong LE, Hodgkinson CA, Yang Y, Sampath H, Ross TJ, Buchholz B, et al. A genetically modulated, intrinsic cingulate circuit supports human nicotine addiction. Proc Natl Acad Sci USA. 2010;107:13509–14. https://doi.org/10.1073/pnas.1004745107.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are thankful to the volunteers, their families, nurses and physicians who helped us to the successful completion of the study. The authors would also like to thank the Department of Clinical Pharmacy and Pharmacology, University of Dhaka, Bangladesh to provide lab facilities and other opportunities to carry out the research work.

Funding

No funding.

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh

    Nusrat Islam Chaity, Taposhi Nahid Sultana, Md. Mehedi Hasan, Noor Ahmed Nahid, Md Saiful Islam & Mohd Nazmul Hasan Apu

  2. Department of Medicine, Mymensingh Medical College Hospital, Mymensingh, 2200, Bangladesh

    Ishrat Islam Shrabonee

Authors
  1. Nusrat Islam Chaity
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Taposhi Nahid Sultana
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Md. Mehedi Hasan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ishrat Islam Shrabonee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Noor Ahmed Nahid
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Md Saiful Islam
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mohd Nazmul Hasan Apu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

N.I.C.: performed all the experiments and drafted the manuscript; T.N.S., M.M.H: assisted in experiments, revised manuscript; I.I.S.: assisted in sample acquisition; N.A.N., S.I.: critically revised manuscript; M.N.H.A.: conceptualized and conceived research design, performed statistical analyses, revised the manuscript, principle investigator.

Corresponding author

Correspondence to Mohd Nazmul Hasan Apu.

Ethics declarations

Conflict of interest

The authors disclose no competing interests.

Ethical standards

The current study was in accordance with the Declaration of Helsinki and its further amendments and the ethical committee of the participating institution approved the study protocol.

Informed consent

Each case and control subject signed an informed consent document after they were informed of the study objectives.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 348 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chaity, N.I., Sultana, T.N., Hasan, M.M. et al. Nicotinic acetylcholine gene cluster CHRNA5-A3-B4 variants influence smoking status in a Bangladeshi population. Pharmacol. Rep 73, 574–582 (2021). https://doi.org/10.1007/s43440-021-00243-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43440-021-00243-1

Keywords

Search

Navigation