Association of M470V polymorphism of CFTR gene with variability of clinical expression of asthma: Case-report study
Main Article Content
Keywords
CFTR gene, M470V polymorphism, Asthma, Tunisian population
Abstract
Introduction and Objectives: Asthma is a complex genetic disorder. Several genes have been found associated with asthma. The cystic fibrosis transmembrane conductance regulator (CFTR) gene is one of them. The aim of this study was to perform a comparative analysis of the genotype and allele frequency distributions of the biallelic marker M470V within the CFTR gene on mutant and wide chromosomes.
Patients and methods: The molecular approach consists in the genotyping of the M470V marker by the PCR-RFLP technique in 105 asthmatic patients, aged between four months and 17 years, and 105 healthy subjects.
Results: We found a significant difference in the genotype frequencies between the two studied groups (2 = 9.855, P = 0.007). The V/V genotype was overrepresented in the asthmatic group as compared to the controls (32.38% vs. 16.19%). Whereas, the M/V genotype is more frequent in healthy subjects (40.95% vs. 28.71%). We also noted a significant difference in allelic distribution of M470V with associated diseases ( 2 = 9.610, P = 0.022).
Conclusions: The present study is the first report on the distribution of the M470V polymorphism in asthmatic Tunisian patients. We noticed that the M470V variant could modulate the clinical phenotype of asthmatic patients. This preliminary study will establish the molecular basis of this disease in Tunisia.
References
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29. Chun XJ, Kotoyo F, Ying S, Ping Z, Nakakuki M, Wei MX, et al. CFTR polymorphisms of healthy individuals in two Chinese cities-Changchun and Nanjing, Nagoya. J Med Sci. 2012;74:293-301.
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31. Chunying L, Anjaparavanda PN. CFTR chloride channel in the apical compartments: spatiotemporal coupling to its interacting partners. Integr Biol (Camb). 2010;2:161-77.
32. Nutan M, Shally A, Pratibha D. Association of CFTR gene mutation with bronchial asthma. Indian J Med Res. 2012;135:469-78.
33. Michoud MC, Robert R, Hassan M, Moynihan B, Haston C, Govindaraju V, et al. Role of the cystic fibrosis transmembrane conductance channel in human airway smooth muscle. Am J Respir Cell Mol Biol. 2009;40:217-22.
34. McCuaig S, Martin JG. How the airway smooth muscle in cystic fibrosis reacts in proinflammatory conditions: implications for airway hyper-responsiveness and asthma in cystic fibrosis. Lancet Respir Med. 2013;1:137-47.
35. Eisner MD, Klein J, Hammond SK, Koren G, Lactao G, Iribarren C. Directly measured second hand smoke exposure and asthma health outcomes. Thorax. 2005;60:814-21.
36. Eisner MD, Yelin EH, Henke J, Shiboski SC, Blanc PD. Environmental tobacco smoke and adult asthma: the impact of changing exposure status on health outcomes. Am J Respir Crit Care Med. 1998;158:170-5.
37. Soussan D, Liard R, Zureik M, Touron D, Rogeaux Y, Neukirch F. Treatment compliance, passive smoking, and asthma control: a three-year cohort study. Arch Dis Child. 2003;88: 229-33.
38. Kim H, Bouchard J, Renzi PM. The link between allergic rhinitis and asthma: a role for antileukotrienes? Can Respir J. 2008;15:91-8.
39. Simons FE. Allergic rhinobronchitis: the asthma-allergic rhinitis link. J Allergy Clin Immunol. 1999;104:534-40.
40. Leynaert B, Neukirch F, Demoly P, Bousquet J. Epidemiologic evidence for asthma and rhinitis comorbidity. J Allergy Clin Immunol. 2000;106:201-5.
41. Spergel JM. Atopic march: link to upper airways. Curr Opin Allergy Clin Immunol. 2005;5:17-21.
42. Gradman J, Wolthers OD. Allergic conjunctivitis in children with asthma, rhinitis and eczema in a secondary outpatient clinic. Pediatr Allergy Immunol. 2006;17:524-6.
2. Makoto K, Yoshiaki I, Ichiro A. Pathology of asthma. Front Microbiol. 2013;4:263.
3. Luke RB, Lorna Z, Walter F, David JE. Epithelial tethering of MUC5AC-rich mucus impairs mucociliary transport in asthma. J Clin Invest. 2016;126:2367-71.
4. Toujani S, Mjid M, Ouahchi Y, Nozha BS, Nadia M, Bechir L, et al. Prevalence of asthma and rhinitis in a Tunisian population. Clin Respir J. 2018;12:608-15.
5. Mahdi B, Padukudru AM, Nallur BR. An understanding of the genetic basis of asthma. Indian J Med Res. 2011;134:149-61.
6. Barnes KC. Genetics and epidemiology. Curr Opin Allergy Clin Immunol. 2002;2:375-8.
7. Dixit P, Awasthi S, Maurya N, Agarwal S, Srinivasan M. CFTR gene mutations and asthma in indian children: a case-control study. Ind J Clin Biochem. 2015;30:35-42.
8. Susan EB, Joy MD, Courtney MF, Katherine LT, Ashley MO. Development of an airway mucus defect in the cystic fibrosis rat. JCI Insight. 2018;3:e97199.
9. Murphy TM, Wong CC, Arseneault L, Burrage J, Macdonald R, Hannon E, et al. Methylomic markers of persistent childhood asthma: a longitudinal study of asthma-discordant monozygotic twins. Clin Epigenet. 2015;7:130.
10. Maurya N, Awasthi S, Dixit P. Association of CFTR gene mutation with bronchial asthma. Indian J Med Res. 2012;135:469-78.
11. De Cid R, Chomel JC, Lazaro C, Sunyer J, Baudis M, Casals T, et al. CFTR and asthma in the French EGEA study. Eur J Hum Genet. 2001;9:67-9.
12. Nikolic A, Divac A, Stankovic M, Dinic J, Tomic B, Ljujic M. Analysis of common CFTR polymorphisms 5T, M470V, and R75Q in healthy Serbian population. Genetika. 2006;42: 996-8.
13. Boudaya M, Hadj Fredj S, Haj RB, Khrouf M, Bouker A, Halouani L, et al. Cystic fibrosis transmembrane conductance regulator mutation and polymorphisms associated with congenital bilateral absence of vas deferens in a restricted group of patients from North Africa. Ann Hum Biol. 2012;39:76-9.
14. Nefzi M, Hadj Fredj S, Tebib N, Barsaoui S, Boussetta K, Siala H, et al. Contribution of M470V variant to cystic fibrosis: first study in CF and normal Tunisian population. Pathol Biol. 2015;63(4-5):169-74.
15. American Lung Association. Lung Disease Data: 2008. New York, NY: American Lung Association, http://www.lung.org/assets/documents/publications/lung-disease data/LDD 2008. pdf; 2008 [accessed 07.01.12].
16. Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, et al. Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med. 2000;161: 309-29.
17. Miller SA, Dyk DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.
18. Romdhane L, Abdelhak S, Research unit on molecular investigation of genetic orphan diseases collaborators. Genetic diseases in the Tunisian population. Am J Med Genet. 2011;155A: 238-67.
19. Du Q, Li Z, Pan Y, Liu X, Pan B, Wu B, et al. M470V, Intron 8 poly-T, and 8 TG-repeats detection in Chinese males with congenital bilateral absence of the Vas Deferens. Biomed Res Int. 2014;2014:689185.
20. Chang MC, Chang YT, Wei SC, Tien YW, Liang PC, Jan IS, et al. Spectrum of mutations and variants/haplotypes of CFTR and genotype-phenotype correlation in idiopathic chronic pancreatitis and controls in Chinese by complete analysis. Clin Genet. 2007;71:530-9.
21. Jin CX, Fujiki K, Song Y, Ping Z, Nakakuki M, Wei MX, et al. CFTR polymorphisms of healthy individuals in two Chinese cities Changchun and Nanjing. Nagoya J Med Sci. 2012;74(3-4):293-301.
22. Ciminelli BM, Bonizzato A, Bombieri C, Pompei F, Gabaldo M, Ciccacci C, et al. Highly preferential association of NonF508del CF mutations with the M470 allele. J Cyst Fibros. 2007;6: 15-22.
23. Wang P, Naruse S, Yin H, Yu Z, Zhuang T, Ding W, et al. The susceptibility of T5-TG12 of the CFTR gene in chronic bronchitis occurrence in a Chinese population in Jiangsu province, China. J Biomed Res. 2012;26:410-7.
24. Kim KW, Lee JH, Lee MG, Kim KH, Sohn MH, Kim KE. Association between cystic fibrosis transmembrane conductance regulator gene mutations and susceptibility for childhood asthma in Korea. Yonsei Med J. 2010;51:912-7.
25. Lázaro C, De Cid R, Sunyer J, Soriano J, Giménez J, Alvarez M, et al. Missense mutations in the cystic fibrosis gene in adult patients with asthma. Hum Mutat. 1999;14:510-9.
26. Hakonarson H, Bjornsdottir US, Ostermann E, Arnason T, Adalsteinsdottir AE, Halapi E, et al. Allelic frequencies and patterns of single-nucleotide polymorphisms in candidate genes for asthma and atopy in Iceland. Am J Respir Crit Care Med. 2001;164:2036-44.
27. Fujiki K, Ishiguro H, Ko SB, Mizuno N, Suzuki Y, Takemura T, et al. Genetic evidence for CFTR dysfunction in Japanese: background for chronic pancreatitis. J Med Genet. 2004;41:e55.
28. Modiano G, Bombieri C, Ciminelli BM, Belpinati F, Giorgi S, Georges Md, et al. A large-scale study of the random variability of a coding sequence: a study on the CFTR gene. Eur J Hum Genet. 2005;13:184-92.
29. Chun XJ, Kotoyo F, Ying S, Ping Z, Nakakuki M, Wei MX, et al. CFTR polymorphisms of healthy individuals in two Chinese cities-Changchun and Nanjing, Nagoya. J Med Sci. 2012;74:293-301.
30. Tzetis M, Efthymiadou A, Strofalis S, Psychou P, Dimakou A, Pouliou E, et al. CFTR gene mutations - including three novel nucleotide substitutions - and haplotype background in patients with asthma, disseminated bronchiectasis and chronic obstructive pulmonary disease. Hum Genet. 2001;108: 216-21.
31. Chunying L, Anjaparavanda PN. CFTR chloride channel in the apical compartments: spatiotemporal coupling to its interacting partners. Integr Biol (Camb). 2010;2:161-77.
32. Nutan M, Shally A, Pratibha D. Association of CFTR gene mutation with bronchial asthma. Indian J Med Res. 2012;135:469-78.
33. Michoud MC, Robert R, Hassan M, Moynihan B, Haston C, Govindaraju V, et al. Role of the cystic fibrosis transmembrane conductance channel in human airway smooth muscle. Am J Respir Cell Mol Biol. 2009;40:217-22.
34. McCuaig S, Martin JG. How the airway smooth muscle in cystic fibrosis reacts in proinflammatory conditions: implications for airway hyper-responsiveness and asthma in cystic fibrosis. Lancet Respir Med. 2013;1:137-47.
35. Eisner MD, Klein J, Hammond SK, Koren G, Lactao G, Iribarren C. Directly measured second hand smoke exposure and asthma health outcomes. Thorax. 2005;60:814-21.
36. Eisner MD, Yelin EH, Henke J, Shiboski SC, Blanc PD. Environmental tobacco smoke and adult asthma: the impact of changing exposure status on health outcomes. Am J Respir Crit Care Med. 1998;158:170-5.
37. Soussan D, Liard R, Zureik M, Touron D, Rogeaux Y, Neukirch F. Treatment compliance, passive smoking, and asthma control: a three-year cohort study. Arch Dis Child. 2003;88: 229-33.
38. Kim H, Bouchard J, Renzi PM. The link between allergic rhinitis and asthma: a role for antileukotrienes? Can Respir J. 2008;15:91-8.
39. Simons FE. Allergic rhinobronchitis: the asthma-allergic rhinitis link. J Allergy Clin Immunol. 1999;104:534-40.
40. Leynaert B, Neukirch F, Demoly P, Bousquet J. Epidemiologic evidence for asthma and rhinitis comorbidity. J Allergy Clin Immunol. 2000;106:201-5.
41. Spergel JM. Atopic march: link to upper airways. Curr Opin Allergy Clin Immunol. 2005;5:17-21.
42. Gradman J, Wolthers OD. Allergic conjunctivitis in children with asthma, rhinitis and eczema in a secondary outpatient clinic. Pediatr Allergy Immunol. 2006;17:524-6.
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Wahabi, I., Hadj Fredj, S., Nefzi, M., Dabboubi, R., Siala, H., Khalsi, F., Bousetta, K., & Messaoud, T. (2019). Association of M470V polymorphism of CFTR gene with variability of clinical expression of asthma: Case-report study. Allergologia Et Immunopathologia, 47(2), 159-165. https://www.all-imm.com/index.php/aei/article/view/339
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Wahabi, I., Hadj Fredj, S., Nefzi, M., Dabboubi, R., Siala, H., Khalsi, F., Bousetta, K., & Messaoud, T. (2019). Association of M470V polymorphism of CFTR gene with variability of clinical expression of asthma: Case-report study. Allergologia Et Immunopathologia, 47(2), 159-165. https://www.all-imm.com/index.php/aei/article/view/339