Yonsei Med J.  2010 Nov;51(6):912-917. 10.3349/ymj.2010.51.6.912.

Association between Cystic Fibrosis Transmembrane Conductance Regulator Gene Mutations and Susceptibility for Childhood Asthma in Korea

• Kim KW
• Lee JH
• Lee MG
• Kim KH
• Sohn MH
• Kim KE

• KMID: 1779639
• DOI: http://doi.org/10.3349/ymj.2010.51.6.912

Abstract

PURPOSE
Classic cystic fibrosis is now known part of cystic fibrosis transmembrane conductance regulator (CFTR)-related disorders. These include a wide spectrum, from multi-system disorders, such as cystic fibrosis, to mono-symptomatic conditions, such as chronic pancreatitis or congenital bilateral absence of the vas deferens. However, respiratory disease is considered typical for the multi system disorder, cystic fibrosis, and is the major cause of morbidity and mortality. The purpose of this study was to evaluate the potential effects of CFTR gene mutations in Korean children with asthma.
MATERIALS AND METHODS
We selected 14 mutations identified in Korea and each of the 48 children with and without asthma were genotyped for the case-control study.
RESULTS
No significant differences were found in genotype and allele frequencies of the 9 polymorphisms observed between the non-asthma and asthma groups. In a haplotype determination based on a Bayesian algorithm, 8 haplotypes were assembled in the 98 individuals tested. However, we also did not find any significant differences in haplotype frequencies between the non-asthma and asthma groups.
CONCLUSION
We have concluded that this study did not show any evidence in support of providing that CFTR genetic variations significantly contribute to the susceptibility of asthma in Korean children.

Keyword

Cystic fibrosis transmembrane conductance regulator; asthma; children

MeSH Terms

Adolescent
Asthma/*epidemiology/*genetics
Case-Control Studies
Child
Cystic Fibrosis Transmembrane Conductance Regulator/*genetics
Female
*Genetic Predisposition to Disease
Genotype
Haplotypes
History, Ancient
Humans
Male
*Mutation
Republic of Korea

Reference

1. Maselli R, Paciocco G. Asthma: pathophysiology of the bronchial obstruction. Allergy. 2000. 55:Suppl 61. 49–51.

2. Shin JW, Sue JH, Song TW, Kim KW, Kim ES, Sohn MH, et al. Atopy and house dust mite sensitization as risk factors for asthma in children. Yonsei Med J. 2005. 46:629–634.

3. Maddox L, Schwartz DA. The pathophysiology of asthma. Annu Rev Med. 2002. 53:477–498.

4. Sengler C, Lau S, Wahn U, Nickel R. Interactions between genes and environmental factors in asthma and atopy: new developments. Respir Res. 2002. 3:7.

5. Nam HS, Lee SY, Kim SJ, Kim JS, Kwon SS, Kim YK, et al. The soluble tumor necrosis factor-alpha receptor suppresses airway inflammation in a murine model of acute asthma. Yonsei Med J. 2009. 50:569–575.

6. Kim SH, Ye YM, Hur GY, Lee HY, Jee YK, Lee SH, et al. Effect of beta2-adrenergic receptor polymorphism in asthma control of patients receiving combination treatment. Yonsei Med J. 2009. 50:182–188.

7. Munthe-Kaas MC, Lødrup Carlsen KC, Carlsen KH, Skinningsrud B, Håland G, Devulapalli CS, et al. CFTR gene mutations and asthma in the Norwegian Environment and Childhood Asthma study. Respir Med. 2006. 100:2121–2128.

8. Moon HR, Ko TS, Ko YY, Choi JH, Kim YC. Cystic fibrosis--a case presented with recurrent bronchiolitis in infancy in a Korean male infant. J Korean Med Sci. 1988. 3:157–162.

9. Ahn KM, Park HY, Lee JH, Lee MG, Kim JH, Kang IJ, et al. Cystic fibrosis in Korean children: a case report identified by a quantitative pilocarpine iontophoresis sweat test and genetic analysis. J Korean Med Sci. 2005. 20:153–157.

10. Koh WJ, Ki CS, Kim JW, Kim JH, Lim SY. Report of a Korean patient with cystic fibrosis, carrying Q98R and Q220X mutations in the CFTR gene. J Korean Med Sci. 2006. 21:563–566.

11. Lee JH, Choi JH, Namkung W, Hanrahan JW, Chang J, Song SY, et al. A haplotype-based molecular analysis of CFTR mutations associated with respiratory and pancreatic diseases. Hum Mol Genet. 2003. 12:2321–2332.

12. Lee KH, Ryu JK, Yoon WJ, Lee JK, Kim YT, Yoon YB. Mutation analysis of SPINK1 and CFTR gene in Korean patients with alcoholic chronic pancreatitis. Dig Dis Sci. 2005. 50:1852–1856.

13. 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. 161:309–329.

14. Sedgwick JB, Vrtis RF, Jansen KJ, Kita H, Bartemes K, Busse WW. Peripheral blood eosinophils from patients with allergic asthma contain increased intracellular eosinophil-derived neurotoxin. J Allergy Clin Immunol. 2004. 114:568–574.

15. Tang K, Ngoi SM, Gwee PC, Chua JM, Lee EJ, Chong SS, et al. Distinct haplotype profiles and strong linkage disequilibrium at the MDR1 multidrug transporter gene locus in three ethnic Asian populations. Pharmacogenetics. 2002. 12:437–450.

16. Niu T, Qin ZS, Xu X, Liu JS. Bayesian haplotype inference for multiple linked single-nucleotide polymorphisms. Am J Hum Genet. 2002. 70:157–169.

17. Mennie M, Gilfillan A, Brock DJ, Liston WA. Heterozygotes for the delta F508 cystic fibrosis allele are not protected against bronchial asthma. Nat Med. 1995. 1:978–979.

18. 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. 9:67–69.

19. Castellani C, Quinzii C, Altieri S, Mastella G, Assael BM. A pilot survey of cystic fibrosis clinical manifestations in CFTR mutation heterozygotes. Genet Test. 2001. 5:249–254.

20. Ngiam NS, Chong SS, Shek LP, Goh DL, Ong KC, Chng SY, et al. Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in Asians with chronic pulmonary disease: a pilot study. J Cyst Fibros. 2006. 5:159–164.

21. 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. 164:2036–2044.

22. Dahl M, Tybjaerg-Hansen A, Lange P, Nordestgaard BG. DeltaF508 heterozygosity in cystic fibrosis and susceptibility to asthma. Lancet. 1998. 351:1911–1913.

23. 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. 108:216–221.

24. Douros K, Loukou I, Doudounakis S, Tzetis M, Priftis KN, Kanavakis E. Asthma and pulmonary function abnormalities in heterozygotes for cystic fibrosis transmembrane regulator gene mutations. Int J Clin Exp Med. 2008. 1:345–349.

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. 14:510–519.

26. Schroeder SA, Gaughan DM, Swift M. Protection against bronchial asthma by CFTR delta F508 mutation: a heterozygote advantage in cystic fibrosis. Nat Med. 1995. 1:703–705.

27. Cuppens H, Teng H, Raeymaekers P, De Boeck C, Cassiman JJ. CFTR haplotype backgrounds on normal and mutant CFTR genes. Hum Mol Genet. 1994. 3:607–614.

28. Dahl M, Nordestgaard BG, Lange P, Tybjaerg-Hansen A. Fifteen-year follow-up of pulmonary function in individuals heterozygous for the cystic fibrosis phenylalanine-508 deletion. J Allergy Clin Immunol. 2001. 107:818–823.

29. Byard PJ, Davis PB. Pulmonary function in obligate heterozygotes for cystic fibrosis. Am Rev Respir Dis. 1988. 138:312–316.