Generic placeholder image

Current Respiratory Medicine Reviews

Editor-in-Chief

ISSN (Print): 1573-398X
ISSN (Online): 1875-6387

Research Article

Association between FOXO3a Gene Polymorphism and Susceptibility to Asthma in South Indian Population

Author(s): Mahendra Maheswarappa*, Manjula Basavaraju, Geetha Bhaktha, Mahesh P. Anand and Nagabushan Seetharama

Volume 19, Issue 2, 2023

Published on: 24 February, 2023

Page: [113 - 121] Pages: 9

DOI: 10.2174/1573398X19666230209101155

Price: $65

Abstract

Background: Asthma is an important cause of morbidity worldwide. The FOXO3a gene plays an important role in human immune regulation and homeostasis. Loss of function may lead to chronic inflammation and asthma.

Objective: To evaluate the association between Foxo3a gene polymorphism and susceptibility to asthma.

Methods: We conducted a case-control study in a tertiary care hospital. Participants answered a questionnaire that collected demographic and clinical information. Asthma was confirmed by pre and post bronchodilator spirometry. Genotyping of the FOXO3a polymorphisms was performed using PCR-RFLP.

Results: The study population included 41 cases and 33 controls. Among cases, the heterozygous (CT) genotype frequency was greater compared to wild homozygous (CC) and mutant homozygous (TT) variants. In controls, the wild homozygous (CC) genotype frequency was greater compared to heterozygous and mutant homozygous variants. In the general model, the mutant homozygous (TT) group had significantly higher odds of 7.8 (1.78-34.07) of having asthma compared to the wild homozygous (CC) group. The mutant homozygous (TT) group had greater severity of asthma as compared to the wild homozygous (CC) group. The mutant homozygous group (TT) had much lower lung functions, as compared to the wild homozygous (CC) group in asthmatics. Among nonasthmatic controls, lower lung functions were seen in the mutant (TT) group as compared to the wild (CC) group.

Conclusion: We found a significant association between the Foxo3a gene polymorphism and asthma. The T allele, a variant of the Foxo3a gene polymorphism, is associated with a higher risk of asthma, and greater asthma severity. It is also associated with lower lung functions in both asthmatics and apparently healthy control subjects.

Keywords: FOXO3a, asthma, single-nucleotide polymorphism, rs13217795, homozygous, wild, mutant, heterozygous, bronchodilator, lung functions, genotyping, frequency.

Graphical Abstract
[1]
Global Initiative for Asthma - GINA Available from: http://ginasthma.org/ (Accessed on: 11 January 2021).
[2]
What is the worldwide prevalence of asthma? Available from: https://www.medscape.com/answers/296301-7945/what-is-the-worldwide-prevalence-of-asthma (Accessed on: 27, January 2021).
[3]
The Global Asthma Report 2018. Available from: http://www. globalasthmareport.org/management/india.php (Accessed on: 11 January 2021).
[4]
Ober C, Hoffjan S. Asthma genetics 2006: the long and winding road to gene discovery. Genes Immun 2006; 7(2): 95-100.
[http://dx.doi.org/10.1038/sj.gene.6364284] [PMID: 16395390]
[5]
Bijanzadeh M, Mahesh PA, Ramachandra NB. An understanding of the genetic basis of asthma. Indian J Med Res 2011; 134(2): 149-61.
[PMID: 21911966]
[6]
Chung KF, Barnes PJ. Cytokines in asthma. Thorax 1999; 54(9): 825-57.
[http://dx.doi.org/10.1136/thx.54.9.825] [PMID: 10456976]
[7]
Gulati K, Guhathakurta S, Joshi J, Rai N, Ray A. Cytokines and their role in health and disease: A brief overview. MOJ Immunol 2016; 4(2): 1-9.
[8]
Nathan C, Ding A. Nonresolving inflammation. Cell 2010; 140(6): 871-82.
[http://dx.doi.org/10.1016/j.cell.2010.02.029] [PMID: 20303877]
[9]
Conti V, Corbi G, Manzo V, Pelaia G, Filippelli A, Vatrella A. Sirtuin 1 and aging theory for chronic obstructive pulmonary disease. Anal Cell Pathol (Amst) 2015; 2015(4): 1-8.
[http://dx.doi.org/10.1155/2015/897327] [PMID: 26236580]
[10]
Lu M, Xu W, Gao B, Xiong S. Blunting autoantigen-induced FOXO3a protein phosphorylation and degradation is a novel pathway of glucocorticoids for the treatment of systemic lupus erythematosus. J Biol Chem 2016; 291(38): 19900-12.
[http://dx.doi.org/10.1074/jbc.M116.728840] [PMID: 27481940]
[11]
Morris BJ, Willcox DC, Donlon TA, Willcox BJ. FOXO3 A major gene for human longevity - a mini-review. Gerontology 2015; 61(6): 515-25.
[http://dx.doi.org/10.1159/000375235] [PMID: 25832544]
[12]
Forkhead box, sub-group O Available from: https://www.sdbonline.org/sites/fly/sturtevant/foxo1.htm (Accessed on: Feb 12,2021).
[13]
Huang H, Tindall DJ. Dynamic FoxO transcription factors. J Cell Sci 2007; 120(15): 2479-87.
[http://dx.doi.org/10.1242/jcs.001222] [PMID: 17646672]
[14]
Barkund S, Shah T, Ambatkar N, Gadgil M, Joshi K. FOXO3a gene polymorphism associated with asthma in Indian population. Mol Biol Int 2015; 2015: 1-6.
[http://dx.doi.org/10.1155/2015/638515] [PMID: 26783460]
[15]
Amarin JZ, Naffa RG, Suradi HH, et al. An intronic single-nucleotide polymorphism (rs13217795) in FOXO3 is associated with asthma and allergic rhinitis: a case–case–control study. BMC Med Genet 2017; 18(1): 132.
[http://dx.doi.org/10.1186/s12881-017-0494-4] [PMID: 29141605]
[16]
Graham BL, Steenbruggen I, Miller MR, et al. Standardization of spirometry 2019 update. An official American thoracic society and European respiratory society technical statement. Am J Respir Crit Care Med 2019; 200(8): e70-88.
[http://dx.doi.org/10.1164/rccm.201908-1590ST] [PMID: 31613151]
[17]
Mahendra M. S SK, Desai N, Bs J, Pa M. Evaluation for airway obstruction in adult patients with stable ischemic heart disease. Indian Heart J 2018; 70(2): 266-71.
[http://dx.doi.org/10.1016/j.ihj.2017.08.003] [PMID: 29716705]
[18]
Elrifai N, Al-Wakeel H, Osman H, El Taweel R. FOXO3a gene polymorphism and bronchial asthma in Egyptian children. Egypt J Pediatr Allergy Immunol 2019; 17(1): 31-6.
[http://dx.doi.org/10.21608/ejpa.2019.41535]
[19]
Kere J, Laitinen T. Positionally cloned susceptibility genes in allergy and asthma. Curr Opin Immunol 2004; 16(6): 689-94.
[http://dx.doi.org/10.1016/j.coi.2004.09.011] [PMID: 15511659]
[20]
Holloway JW, Yang IA, Holgate ST. Genetics of allergic disease. J Allergy Clin Immunol 2010; 125(2) (Suppl. 2): S81-94.
[http://dx.doi.org/10.1016/j.jaci.2009.10.071] [PMID: 20176270]
[21]
Howard TD, Meyers DA, Bleecker ER. Mapping susceptibility genes for allergic diseases. Chest 2003; 123(3) (Suppl.): 363S-8S.
[http://dx.doi.org/10.1378/chest.123.3_suppl.363S-a] [PMID: 12628976]
[22]
Willis-Owen SAG, Cookson WO, Moffatt MF. Genome-wide association studies in the genetics of asthma. Curr Allergy Asthma Rep 2009; 9(1): 3-9.
[http://dx.doi.org/10.1007/s11882-009-0001-x] [PMID: 19063818]
[23]
Cookson W. The alliance of genes and environment in asthma and allergy. Nature 1999; 402(S6760) (Suppl.): 5-11.
[http://dx.doi.org/10.1038/35037002] [PMID: 10586889]
[24]
Goodi Ghaidaa Abdul Kareem. AL-Saadi Basima Qasim. Polymorphism of foxo3a gene and its association with incidence of asthma in Iraqi patients. Iran J Biotechnol 2018; 7(3): 67-77.
[25]
Caslin HL, Kiwanuka KN, Haque TT, et al. Controlling mast cell activation and homeostasis: work influenced by bill paul that continues today. Front Immunol 2018; 9: 868.
[http://dx.doi.org/10.3389/fimmu.2018.00868] [PMID: 29755466]
[26]
Oda JMM, Hirata BKB, Guembarovski RL, Watanabe MAE. Genetic polymorphism in FOXP3 gene: Imbalance in regulatory T-cell role and development of human diseases. J Genet 2013; 92(1): 163-71.
[http://dx.doi.org/10.1007/s12041-013-0213-7] [PMID: 23640423]
[27]
Peng SL. Forkhead transcription factors in chronic inflammation. Int J Biochem Cell Biol 2010; 42(4): 482-5.
[http://dx.doi.org/10.1016/j.biocel.2009.10.013] [PMID: 19850149]
[28]
Malik S, Sadhu S, Elesela S, et al. Transcription factor Foxo1 is essential for IL-9 induction in T helper cells. Nat Commun 2017; 8(1): 815.
[http://dx.doi.org/10.1038/s41467-017-00674-6] [PMID: 28993609]
[29]
Graves DT, Milovanova TN. Mucosal immunity and the FOXO1 transcription factors. Front Immunol 2019; 10: 2530.
[http://dx.doi.org/10.3389/fimmu.2019.02530] [PMID: 31849924]
[30]
Kany S, Vollrath JT, Relja B. Cytokines in inflammatory disease. Int J Mol Sci 2019; 20(23): 6008.
[http://dx.doi.org/10.3390/ijms20236008] [PMID: 31795299]
[31]
Yuan L, Wang L, Du X, et al. The DNA methylation of FOXO3 and TP53 as a blood biomarker of late-onset asthma. J Transl Med 2020; 18(1): 467.
[http://dx.doi.org/10.1186/s12967-020-02643-y] [PMID: 33298101]
[32]
Palumbo F, Seeger W, Morty RE. The role of FoxO transcription factors in normal and aberrant late lung development. Eur Respir J 2017; 50: PA2088.
[33]
Tsai MJ, Tsai YC, Chang WA, et al. Deducting MicroRNA-mediated changes common in bronchial epithelial cells of asthma and chronic obstructive pulmonary disease-a next-generation sequencing-guided bioinformatic approach. Int J Mol Sci 2019; 20(3): 553.
[http://dx.doi.org/10.3390/ijms20030553] [PMID: 30696075]

Rights & Permissions Print Export Cite as
© 2024 Bentham Science Publishers | Privacy Policy