Skip to main content
Top
Published in: European Journal of Pediatrics 12/2009

01-12-2009 | Original Paper

Involvement of FcɛR1β gene polymorphisms in susceptibility to atopy in Korean children with asthma

Authors: Eun Soo Kim, Seung-Hyun Kim, Kyung Won Kim, Hae-Sim Park, Eun Soon Shin, Jong Eun Lee, Myung Hyun Sohn, Kyu-Earn Kim

Published in: European Journal of Pediatrics | Issue 12/2009

Login to get access

Abstract

Introduction

IgE-dependent activation of mast cells and basophils through the high-affinity IgE receptor (FcɛR1) is involved in the pathogenesis of allergen-induced immune responsiveness in atopic disease including bronchial asthma.

Materials and methods

We genotyped 650 children for allelic determinants at two polymorphic sites, −109T/C and E237G, in the FcɛR1β gene by SNP-IT™ assays using the SNP stream 25K™ system.

Results

Distributions of the genotype and allele frequencies of FcɛR1β −109T/C and E237G polymorphisms were significantly associated with atopy (P < 0.05) and elevated serum IgE levels. However, differences in the E237G polymorphism did not reach statistical significance after adjustment for multiple comparisons. The genotypes TC or CC at −109T/C were associated with decreased forced expiratory flow25–75% in children with asthma (P < 0.05), but this did not reach statistical significance after correction for multiple comparisons. In addition, haplotype 1 (T-A) was associated with atopy susceptibility (P = 0.0069). Analysis of genotype distributions of haplotypes demonstrated a significantly lower PC20 for homozygous −/− diploids compared with homozygous Ht1/Ht1 (P = 0.0261).

Conclusion

Polymorphisms in the FcɛR1β gene confer susceptibility to atopy in Korean children and may have a disease-modifying effect on airways of asthmatic patients.
Literature
5.
go back to reference Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, MacIntyre NR, McKay RT, Wanger JS, Anderson SD, Cockcroft DW, Fish JE, Sterk PJ (2000) 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 161:309–329PubMed Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, MacIntyre NR, McKay RT, Wanger JS, Anderson SD, Cockcroft DW, Fish JE, Sterk PJ (2000) 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 161:309–329PubMed
6.
go back to reference Daniels SE, Bhattacharrya W, James A, Leaves NI, Young A, Hill MR, Faux JA, Ryan GF, le Souef PN, Lathrop GM, Musk AW, Cookson WO (1996) A genome-wide search for quantitative trait loci underlying asthma. Nature 383:247–250 doi:10.1038/383247a0 CrossRefPubMed Daniels SE, Bhattacharrya W, James A, Leaves NI, Young A, Hill MR, Faux JA, Ryan GF, le Souef PN, Lathrop GM, Musk AW, Cookson WO (1996) A genome-wide search for quantitative trait loci underlying asthma. Nature 383:247–250 doi:10.​1038/​383247a0 CrossRefPubMed
7.
go back to reference Hedrick PW (1987) Gametic disequilibrium measures: proceed with caution. Genetics 117:331–341PubMed Hedrick PW (1987) Gametic disequilibrium measures: proceed with caution. Genetics 117:331–341PubMed
8.
go back to reference Hill MR, Cookson WO (1996) A new variant of the β subunits of the high-affinity receptor for immunoglobulin E (FcɛR1-β E237G): associations with measures of atopy and bronchial hyperresponsiveness. Hum Mol Genet 5:959–962 doi:10.1093/hmg/5.7.959 CrossRefPubMed Hill MR, Cookson WO (1996) A new variant of the β subunits of the high-affinity receptor for immunoglobulin E (FcɛR1-β E237G): associations with measures of atopy and bronchial hyperresponsiveness. Hum Mol Genet 5:959–962 doi:10.​1093/​hmg/​5.​7.​959 CrossRefPubMed
9.
go back to reference Hill MR, James AL, Faux JA, Ryan G, Hopkin JM, le Souef P, Musk AW, Cookson WO (1995) Fc epsilon RI-beta polymorphism and risk of atopy in a general population sample. BMJ 311:776–779PubMed Hill MR, James AL, Faux JA, Ryan G, Hopkin JM, le Souef P, Musk AW, Cookson WO (1995) Fc epsilon RI-beta polymorphism and risk of atopy in a general population sample. BMJ 311:776–779PubMed
11.
go back to reference Hizawa N, Yamaguchi E, Furuya K, Ohnuma N, Kodama N, Kojima J, Ohe M, Kawakami Y (1995) Association between high serum total IgE levels and D11S97 on chromosome 11q13 in Japanese subjects. J Med Genet 32:363–369 doi:10.1136/jmg.32.5.363 CrossRefPubMed Hizawa N, Yamaguchi E, Furuya K, Ohnuma N, Kodama N, Kojima J, Ohe M, Kawakami Y (1995) Association between high serum total IgE levels and D11S97 on chromosome 11q13 in Japanese subjects. J Med Genet 32:363–369 doi:10.​1136/​jmg.​32.​5.​363 CrossRefPubMed
12.
go back to reference Hizawa N, Yamaguchi E, Jinushi E, Kawakami Y (2000) A common FCER1B gene promoter polymorphism influences total serum IgE levels in a Japanese population. Am J Respir Crit Care Med 161:906–909PubMed Hizawa N, Yamaguchi E, Jinushi E, Kawakami Y (2000) A common FCER1B gene promoter polymorphism influences total serum IgE levels in a Japanese population. Am J Respir Crit Care Med 161:906–909PubMed
13.
17.
go back to reference Mao XQ, Shirakawa T, Yoshikawa T, Yoshikawa K, Kawai M, Sasaki S, Enomoto T, Hashimoto T, Furuyama J, Hopkin JM, Morimoto K (1996) Association between genetic variants of mast-cell chymase and eczema. Lancet 348:581–583 doi:10.1016/S0140-6736(95)10244-2 CrossRefPubMed Mao XQ, Shirakawa T, Yoshikawa T, Yoshikawa K, Kawai M, Sasaki S, Enomoto T, Hashimoto T, Furuyama J, Hopkin JM, Morimoto K (1996) Association between genetic variants of mast-cell chymase and eczema. Lancet 348:581–583 doi:10.​1016/​S0140-6736(95)10244-2 CrossRefPubMed
19.
go back to reference Nagata H, Mutoh H, Kumahara K, Arimoto Y, Tomemori T, Sakurai D, Arase K, Ohno K, Yamakoshi T, Nakano K, Okawa T, Numata T, Konno A (2001) Association between nasal allergy and a coding variant of the Fc epsilon RI beta gene Glu237Gly in a Japanese population. Hum Genet 109:262–266 doi:10.1007/s004390100561 CrossRefPubMed Nagata H, Mutoh H, Kumahara K, Arimoto Y, Tomemori T, Sakurai D, Arase K, Ohno K, Yamakoshi T, Nakano K, Okawa T, Numata T, Konno A (2001) Association between nasal allergy and a coding variant of the Fc epsilon RI beta gene Glu237Gly in a Japanese population. Hum Genet 109:262–266 doi:10.​1007/​s004390100561 CrossRefPubMed
20.
go back to reference Nishiyama C, Akizawa Y, Nishiyama N, Tokura T, Kawada H, Mitsuishi K, Hasegawa M, Ito T, Nakano N, Okamoto A, Takagi A, Yagita H, Okumura K, Ogawa H (2004) Polymorphisms in the Fc epsilon RI beta promoter region affecting transcription activity: a possible promoter-dependent mechanism for association between Fc epsilon RI beta and atopy. J Immunol 173:6458–6464PubMed Nishiyama C, Akizawa Y, Nishiyama N, Tokura T, Kawada H, Mitsuishi K, Hasegawa M, Ito T, Nakano N, Okamoto A, Takagi A, Yagita H, Okumura K, Ogawa H (2004) Polymorphisms in the Fc epsilon RI beta promoter region affecting transcription activity: a possible promoter-dependent mechanism for association between Fc epsilon RI beta and atopy. J Immunol 173:6458–6464PubMed
22.
go back to reference Palmer LJ, Pare PD, Faux JA, Moffatt MF, Daniels SE, LeSouef PN, Bremner PR, Mockford E, Gracey M, Spargo R, Musk AW, Cookson WO (1997) Fc epsilon R1-beta polymorphism and total serum IgE levels in endemically parasitized Australian aborigines. Am J Hum Genet 61:182–188 doi:10.1086/513888 CrossRefPubMed Palmer LJ, Pare PD, Faux JA, Moffatt MF, Daniels SE, LeSouef PN, Bremner PR, Mockford E, Gracey M, Spargo R, Musk AW, Cookson WO (1997) Fc epsilon R1-beta polymorphism and total serum IgE levels in endemically parasitized Australian aborigines. Am J Hum Genet 61:182–188 doi:10.​1086/​513888 CrossRefPubMed
23.
go back to reference Sedgwick JB, Vrtis RF, Jansen KJ, Kita H, Bartemes K, Busse WW (2004) Peripheral blood eosinophils from patients with allergic asthma contain increased intracellular eosinophil-derived neurotoxin. J Allergy Clin Immunol 114:568–574 doi:10.1016/j.jaci.2004.05.023 CrossRefPubMed Sedgwick JB, Vrtis RF, Jansen KJ, Kita H, Bartemes K, Busse WW (2004) Peripheral blood eosinophils from patients with allergic asthma contain increased intracellular eosinophil-derived neurotoxin. J Allergy Clin Immunol 114:568–574 doi:10.​1016/​j.​jaci.​2004.​05.​023 CrossRefPubMed
24.
25.
go back to reference Shirakawa T, Li A, Dubowitz M, Dekker JW, Shaw AE, Faux JA, Ra C, Cookson WO, Hopkin JM (1994) Association between atopy and variants of the β subunit of the high affinity immunoglobulin E receptor. Nat Genet 7:125–129 doi:10.1038/ng0694-125 CrossRefPubMed Shirakawa T, Li A, Dubowitz M, Dekker JW, Shaw AE, Faux JA, Ra C, Cookson WO, Hopkin JM (1994) Association between atopy and variants of the β subunit of the high affinity immunoglobulin E receptor. Nat Genet 7:125–129 doi:10.​1038/​ng0694-125 CrossRefPubMed
26.
go back to reference Shirakawa T, Mao XQ, Sasaki S, Enomoto T, Kawai M, Morimoto K, Hopkin J (1996) Association between atopic asthma and a coding variant of Fc epsilon RI beta in a Japanese population. Hum Mol Genet 5:1129–1130 doi:10.1093/hmg/5.8.1129 CrossRefPubMed Shirakawa T, Mao XQ, Sasaki S, Enomoto T, Kawai M, Morimoto K, Hopkin J (1996) Association between atopic asthma and a coding variant of Fc epsilon RI beta in a Japanese population. Hum Mol Genet 5:1129–1130 doi:10.​1093/​hmg/​5.​8.​1129 CrossRefPubMed
27.
go back to reference Stanford AJ, Shirakawa T, Moffatt MF, Daniels SE, Ra C, Faux JA, Young RP, Nakamura Y, Lathrop GM, Cookson WO, Hopkin JM (1993) Localisation of atopy and β subunit of high-affinity IgE receptor (FcɛR1) on chromosome 11q. Lancet 341:332–334 doi:10.1016/0140-6736(93)90136-5 CrossRef Stanford AJ, Shirakawa T, Moffatt MF, Daniels SE, Ra C, Faux JA, Young RP, Nakamura Y, Lathrop GM, Cookson WO, Hopkin JM (1993) Localisation of atopy and β subunit of high-affinity IgE receptor (FcɛR1) on chromosome 11q. Lancet 341:332–334 doi:10.​1016/​0140-6736(93)90136-5 CrossRef
Metadata
Title
Involvement of FcɛR1β gene polymorphisms in susceptibility to atopy in Korean children with asthma
Authors
Eun Soo Kim
Seung-Hyun Kim
Kyung Won Kim
Hae-Sim Park
Eun Soon Shin
Jong Eun Lee
Myung Hyun Sohn
Kyu-Earn Kim
Publication date
01-12-2009
Publisher
Springer-Verlag
Published in
European Journal of Pediatrics / Issue 12/2009
Print ISSN: 0340-6199
Electronic ISSN: 1432-1076
DOI
https://doi.org/10.1007/s00431-009-0960-x

Other articles of this Issue 12/2009

European Journal of Pediatrics 12/2009 Go to the issue