Abstract
Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease of the respiratory system. Smoking is a major risk factor of COPD. Neurotransmitter system genes were tested for association with COPD using DNA samples from COPD patients (N = 601) and healthy subjects (N = 617). SNPs of GRIK3 (rs534131), GRIN2B (rs7301328 and rs1805476), GRIA1 (rs2195450), GRIN1 (rs6293), GABBR2 (rs3750344), BDNF (rs6265 and rs11030107), and ANKK1 (rs1800497) were genotyped by real-time polymerase chain reaction (PCR). Significant associations were detected for GRIK3 (rs534131) (P = 0.009, OR = 1.42 in a dominant model), GRIA1 (rs2195450) (P = 0.015, OR = 1.35 in a dominant model), GRIN1 (rs6293) (P = 0.036, OR = 0.79 in a log-additive model), and GRIN2B (rs7301328) (P = 0.0009, OR = 0.54 in a recessive model). GRIK3 (rs534131) (P = 0.0001, OR = 1.68 in a dominant model) and GRIN2B (rs7301328) (P = 0.001, OR = 0.52 in a recessive model) were significantly associated with COPD only in smokers. Associations of GRIN1 (rs6293) (P = 0.0001, OR = 0.36 in a dominant model), GRIA1 (rs2195450) (P = 0.0018, OR = 2.40 in a log-additive model), and BDNF (rs11030107) (P = 0.005, OR = 2.86 for TT) with COPD were detected in nonsmokers. Lower smoking index were observed in carriers of the GRIK3 (rs534131) genotype GG and GRIA1 (rs2195450) genotype GG (P = 0.028 and 0.0001, respectively). The level of nicotine dependence was significantly higher in carriers of the rare allele A of GRIK3 (rs534131A>G) and the genotype GC of GRIN2B (rs7301328C>G) (P = 0.011 and 0.023, respectively). Informative genotype and allele combinations significantly associated with COPD were identified using the APSampler algorithm and included GRIN2B rs2268132*T, GRIN2B rs7301328*G, GRIN2B rs1805476*C, ANKK1 rs1800497*G, GABBR2 rs3750344*A, CHRNA5 rs16969968*T, CHRNA3 rs1051730*A, HTR2A rs6313*CC, and GRIA1 rs2195450*G.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Explore related subjects
Discover the latest articles and news from researchers in related subjects, suggested using machine learning.REFERENCES
From the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD), 2017. http://goldcopd.org.
Broms, U., Silventoinen, K., Madden, P.A., et al., Genetic architecture of smoking behavior: a study of Finnish adult twins, Twin Res. Hum. Genet., 2006, vol. 9, no. 1, pp. 64–72. https://doi.org/10.1375/183242706776403046
Bierut, L.J., Nicotine dependence and genetic variation in the nicotinic receptors, Drug Alcohol Depend., 2009, vol. 104, suppl. 1, pp. S64–S69. https://doi.org/10.1016/j.drugalcdep.2009.06.003
Tobacco and Genetics Consortium, Genome-wide meta-analyses identify multiple loci associated with smoking behavior, Nat. Genet., 2010, vol. 42, no. 5, pp. 441–447. https://doi.org/10.1038/ng.571
Bierut, L.J., Convergence of genetic findings for nicotine dependence and smoking related diseases with chromosome 15q24-25, Trends Pharmacol. Sci., 2010, vol. 31, no. 1, pp. 46–51. https://doi.org/10.1016/j.tips.2009.10.004
Wolock, S.L., Yates, A., Petrill, S.A., et al., Gene × smoking interactions on human brain gene expression: finding common mechanisms in adolescents and adults, J. Child. Psychol. Psychiatry, 2013, vol. 54, no. 10, pp. 1109–1119. https://doi.org/10.1111/jcpp.12119
Korytina, G.F., Akhmadishina, L.Z., Viktorova, E.V., et al., IREB2, CHRNA5, CHRNA3, FAM13A and hedgehog interacting protein genes polymorphisms and risk of chronic obstructive pulmonary disease in Tatar population from Russia, Indian J. Med. Res., 2016, vol. 144, no. 6, pp. 865–876. https://doi.org/10.4103/ijmr.IJMR_1233_14
Korytina, G.F., Akhmadishina, L.Z., Kochetova, O.V., et al., Polymorphic variants of glutamate receptor (GRIK5, GRIN2B) and serotonin receptor (HTR2A) genes are associated with chronic obstructive pulmonary disease, Mol. Biol., 2017, vol. 51, no. 4, pp. 533–542. https://doi.org/10.1134/S0026893317040124
The National Center for Biotechnology Information advances science and health by providing access to biomedical and genomic information (US). http://www.ncbi.nlm.nih.gov/projects/SNP/.
Ward, L.D. and Kellis, M., HaploReg v4: systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease, Nucleic Acids Res., 2016, vol. 44, no. D1, pp. D877–D881. https://doi.org/10.1093/nar/gkv1340
Purcell, S., Neale, B., Todd-Brown, K., et al., PLINK: a toolset for whole-genome association and population-based linkage analysis, Am. J. Hum. Genet., 2007, vol. 81, no. 3, pp. 559–575. https://doi.org/10.1086/519795
Favorov, A.V., Andreewski, T.V., Sudomoina, M.A., et al., A Markov chain Monte Carlo technique for identification of combinations of allelic variants underlying complex diseases in humans, Genetics, 2005, vol. 171, no. 4, pp. 2113–2121. https://doi.org/10.1534/genetics.105.048090
Smith, D.J., Escott-Price, V., Davies, G., et al., Genome-wide analysis of over 106 000 individuals identifies 9 neuroticism-associated loci, Mol. Psychiatry, 2016, vol. 21, no. 6, pp. 749–757. https://doi.org/10.1038/mp.2016.49
Grucza, R.A., Johnson, E.O., Krueger, R.F., et al., Incorporating age at onset of smoking into genetic models for nicotine dependence: evidence for interaction with multiple genes, Addict. Biol., 2010, vol. 15, no. 3, pp. 346–357. https://doi.org/10.1111/j.1369-1600.2010.00220.x
Vink, J.M., Smit, A.B., de Geus, E.J., et al., Genome-wide association study of smoking initiation and current smoking, Am. J. Hum. Genet., 2009, vol. 84, no. 3, pp. 367–379. https://doi.org/10.1016/j.ajhg.2009.02.001
Orihara, K., Odemuyiwa, S.O., Stefura, W.P., et al., Neurotransmitter signalling via NMDA receptors leads to decreased T helper type 1-like and enhanced T helper type 2-like immune balance in humans, Immunology, 2018, vol. 153, no. 3, pp. 368–379. https://doi.org/10.1111/imm.12846
Jamal, M., Van der Does, W., Elzinga, B.M., et al., Association between smoking, nicotine dependence, and BDNF Val66Met polymorphism with BDNF concentrations in serum, Nicotine Tob. Res., 2015, vol. 17, no. 3, pp. 323–329. https://doi.org/10.1093/ntr/ntu151
Ohmoto, M. and Takahashi, T., Effect of genetic polymorphism of brain-derived neurotrophic factor and serotonin transporter on smoking phenotypes: a pilot study of Japanese participants, Heliyon, 2019, vol. 5, no. 2. e01234. https://doi.org/10.1016/j.heliyon.2019.e01234
Beuten, J., Ma, J.Z., Payne, T.J., et al., Single- and multilocus allelic variants within the GABA(B) receptor subunit 2 (GABAB2) gene are significantly associated with nicotine dependence, Am. J. Hum. Genet., 2005, vol. 76, no. 5, pp. 859–864. https://doi.org/10.1086/429839
Cui, W.Y., Seneviratne, C., Gu, J., et al., Genetics of GABAergic signaling in nicotine and alcohol dependence, Hum. Genet., 2012, vol. 131, no. 6, pp. 843–855. https://doi.org/10.1007/s00439-011-1108-4
Dani, J.A., Roles of dopamine signaling in nicotine addiction, Mol. Psychiatry, 2003, vol. 8, no. 3, pp. 255–256. https://doi.org/10.1038/sj.mp.4001284
Neville, M.J., Johnstone, E.C., and Walton, R.T., Identification and characterization of ANKK1: a novel kinase gene closely linked to DRD2 on chromosome band 11q23.1, Hum. Mutat., 2004, vol. 23, no. 6, pp. 540–545. https://doi.org/10.1002/humu.20039
Koeneke, A., Ponce, G., Troya-Balseca, J., et al., Ankyrin repeat and kinase domain containing 1 gene, and addiction vulnerability, Int. J. Mol. Sci., 2020, vol. 21, no. 7, p. 2516. https://doi.org/10.3390/ijms21072516
Liu, Q., Xu, Y., Mao, Y., et al., Genetic and epigenetic analysis revealing variants in the NCAM1-TTC12-ANKK1-DRD2 cluster associated significantly with nicotine dependence in Chinese Han smokers, Nicotine Tob. Res., 2020, vol. 22, no. 8, pp. 1301–1309. https://doi.org/10.1093/ntr/ntz240
ACKNOWLEDGMENTS
This study was carried out using equipment of the Biomika Shared Access Center and KODINK Unique Research System (Institute of Biochemistry and Genetics).
Funding
The study was supported by research project no. AAAA-A21-121011990119-1. Biological material (DNA samples) for the study were obtained from the Collection of Human Biological Materials (Institute of Biochemistry and Genetics), which was supported by the Bioresource Collection Program of the Federal Agency for Scientific Organizations of Russia.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest. The authors declare that they have no conflict of interest.
Statement of compliance with standards of research involving humans as subjects. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants involved in the study.
Additional information
Translated by T. Tkacheva
Rights and permissions
About this article
Cite this article
Korytina, G.F., Akhmadishina, L.Z., Kochetova, O.V. et al. Role of Neurotransmitter System Genes in Chronic Obstructive Pulmonary Disease. Russ J Genet 57, 1294–1303 (2021). https://doi.org/10.1134/S1022795421110065
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1022795421110065