Archives of Advances in Biosciences

Vol. 16 No. 1 (2025)

The Study of the Association in between CHRNA 5 Gene Polymorphism (rs16969968) and Chronic Obstructive Pulmonary Disease

Archives of Advances in Biosciences, Vol. 16 No. 1 (2025), 2 March 2025 , Page 1-7
https://doi.org/10.22037/aab.v16i1.51287

Abstract

Background and Aim: Chronic obstructive pulmonary disease (COPD) is a complex, progressive inflammatory disorder of the respiratory system that predominantly affects the distal airways and is characterized by irreversible destruction of lung parenchyma. Genetic susceptibility plays an important role in the pathogenesis of COPD. The objective of this study was to examine the relationship between COPD and CHRNA5 gene polymorphism (rs16969968).

Methods: A total of 200 subjects were enrolled, including 100 diagnosed COPD cases and 100 age- and sex-matched healthy controls. Genotyping of the single nucleotide polymorphism (SNP) rs16969968 was carried out using allele-specific polymerase chain reaction (AS-PCR) with specific primers. Allele and genotype frequencies were measured, and statistical analysis was conducted using SPSS software to assess the association between CHRNA5 gene polymorphism and COPD risk.

Results: The distribution of CHRNA5 (rs16969968) genotypes did not show a statistically significant association with COPD. The AA genotype was observed in 6% of controls and 15% of COPD cases, the heterozygous AG genotype in 39% of controls and 43% of COPD patients, and the homozygous GG genotype in 55% of controls and 42% of COPD cases. The wild-type G allele was found in 149 (74.5%) of controls and 127 (63.5%) of COPD patients, while the A allele was found in 51 (25.5%) of controls and 73 (36.5%) of COPD cases. Statistical analysis revealed no significant difference in allele frequencies (p = 0.157). Although genotype distribution showed a trend toward significance (p = 0.055), it did not reach the conventional threshold (p < 0.05). Odds ratio analysis revealed an OR of 1.688 (p = 0.066), suggesting a possible increased risk among A allele carriers.

Conclusion: This study did not demonstrate association between the CHRNA5 rs16969968 polymorphism and COPD. However, odds ratio analysis indicated a possible 1.7-fold increased risk of COPD among carriers of the A allele, suggesting a potential role of CHRNA5 variants in disease susceptibility. Larger studies with diverse populations are warranted to further clarify the contribution of CHRNA5 variants to COPD risk.

Keywords:
  • Chronic obstructive pulmonary disease
  • Polymorphism
  • Single Nucleotide
  • Genotype
  • Alleles
  • Smoking
  • Tuberculosis
  • Polymerase Chain Reaction

How to Cite

Aggarwal, J., & Sharma, B. (2026). The Study of the Association in between CHRNA 5 Gene Polymorphism (rs16969968) and Chronic Obstructive Pulmonary Disease . Archives of Advances in Biosciences, 16(1), 1–7. https://doi.org/10.22037/aab.v16i1.51287

References

1. Barnes PJ, Burney PG, Silverman EK, Celli BR, Vestbo J, Wedzicha JA, et al. Chronic obstructive pulmonary disease. New England Journal of Medicine. 2000 Dec;343:269–280. (DOI: 10.1038/nrdp.2015.76) (PMID)

2. American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine. 1995 Nov;152(5 Pt 2):S77–S121. (PMID)

3. Murray CJ, Lopez AD. Alternative projection of mortality and disability by cause 1990–2020: Global Burden of Disease Study. Lancet. 1997 May;349:1498–1504. (DOI: 10.1016/S0140-6736(96)07492-2) (PMID)

4. National Heart, Lung, and Blood Institute. Data Fact Sheet: Chronic Obstructive Pulmonary Disease. NIH Publication No. 03-5229. Bethesda (MD): U.S. Department of Health and Human Services; 2003. (LINK)

5. Mannino DM. COPD: epidemiology, prevalence, morbidity and mortality, and disease heterogeneity. Chest. 2002 May;121(5 Suppl):121S–126S. (DOI: 10.1378/chest.121.5_suppl.121s) (PMID)

6. Barnes PJ. Small airways in COPD. New England Journal of Medicine. 2004 Jun;350:2635–2637. (DOI: 10.1056/NEJMp048102) (PMID)

7. Barnes PJ. Mechanisms in COPD: differences from asthma. Chest. 2000 Feb;117(2 Suppl):10S–14S. (DOI: 10.1378/chest.117.2_suppl.10s) (PMID)

8. Zhang PD, Zhang XR, Zhang A, Li ZH, Liu D, Zhang YJ, et al. Associations of genetic risk and smoking with incident COPD. European Respiratory Journal. 2022 Feb;59(2):2101320. (DOI: 10.1183/13993003.01320-2021) (PMID)

9. Yang L, Yang Z, Zuo C, Lv X, Liu T, Jia C, et al. Epidemiological evidence for associations between variants in CHRNA genes and risk of lung cancer and chronic obstructive pulmonary disease. Frontiers in Oncology. 2022 Oct;12:1001864. (DOI: 10.3389/fonc.2022.1001864) (PMID)

10. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of COPD: 2024 Report. GOLD; 2024. (Link)

11. Vestbo J, Hurd SS, Agustí AG, Jones PW, Vogelmeier C, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013 Feb;187(4):347-65. (DOI: 10.1164/rccm.201204-0596PP) (PMID)

12. World Health Organization. Chronic obstructive pulmonary disease (COPD). WHO; 2024. (Link)

13. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLOS Medicine. 2006 Nov;3(11):e442. (DOI: 10.1371/journal.pmed.0030442) (PMID)

14. Salvi SS, Barnes PJ. Chronic obstructive pulmonary disease in non-smokers. Lancet. 2009 Aug;374(9691):733–43. (DOI: 10.1016/S0140-6736(09)61303-9) (PMID)

15. Eisner MD, Anthonisen N, Coultas D, Kuenzli N, Perez-Padilla R, Postma D, et al. Novel risk factors and the global burden of chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine. 2010 Sep;182(5):693–718. (DOI: 10.1164/rccm.200811-1757ST) (PMID)

16. DeMeo DL, Silverman EK. Genetics of chronic obstructive pulmonary disease. Semin Respir Crit Care Med. 2003 Apr;24(2):151-60. (DOI: 10.1055/s-2003-39014). (PMID).

17. DeMeo DL, Silverman EK. Genetics of chronic obstructive pulmonary disease. Seminars in Respiratory and Critical Care Medicine. 2003 Apr;24(2):151-60. (DOI: 10.1055/s-2003-39014) (PMID)

18. Kaur-Knudsen D, Nordestgaard BG, Bojesen SE. CHRNA3 genotype, nicotine dependence, lung function and disease in the general population. European Respiratory Journal. 2012 Nov 30;40(6):1538-44. (DOI: 10.1183/09031936.00176811).

19. 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 genes. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2009 Jun;150B(4):453–466. (DOI: 10.1002/ajmg.b.30828) (PMID)

20. Wang JC, Cruchaga C, Saccone NL, Bertelsen S, Liu P, Budde JP, et al. Risk for nicotine dependence and lung cancer is conferred by mRNA expression levels and amino acid change in CHRNA5. Human Molecular Genetics. 2009 Aug;18(16):3125–35. (DOI: 10.1093/hmg/ddp231) (PMID)

21. 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 Apr;452(7187):638–42. (DOI: 10.1038/nature06846) (PMID)

22. Pillai SG, Ge D, Zhu G, Kong X, Shianna KV, Need AC, et al. A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major susceptibility loci. PLoS Genetics. 2009 Mar;5(3):e1000421. (DOI: 10.1371/journal.pgen.1000421) (PMID)

23. Cho MH, McDonald ML, Zhou X, Mattheisen M, Castaldi PJ, Hersh CP, et al. Risk loci for chronic obstructive pulmonary disease: a genome-wide association study and meta-analysis. Lancet Respiratory Medicine. 2015 Mar;2(3):214–25. (DOI: 10.1016/S2213-2600(14)70002-5) (PMID)

24. Wilk JB, Shrine NR, Loehr LR, Zhao JH, Manichaikul A, Lopez LM, et al. Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction. American Journal of Respiratory and Critical Care Medicine. 2012 Oct;186(7):622–32. (DOI: 10.1164/rccm.201202-0366OC) (PMID)

25. Bierut LJ, Stitzel JA, Wang JC, Hinrichs AL, Grucza RA, Xuei X, et al. Variants in nicotinic receptors and risk for nicotine dependence. American Journal of Psychiatry. 2008 Sep;165(9):1163–71. (DOI: 10.1176/appi.ajp.2008.07111711) (PMID)

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