Allergy, Asthma & Respiratory Disease

대한천식알레르기학회 (The Korean Academy of Asthma, Allergy and Clinical Immunology)
권호 표지
DOI QR코드

DOI QR Code

한국 소아 알레르기질환의 유전학적 연구 현황과 과제

Overview and challenges of current genetic research on allergic diseases in Korean children

  • 손명현 (연세대학교 의과대학 소아과학교실)
  • Sohn, Myunghyun (Department of Pediatrics, Yonsei University College of Medicine)
  • 투고 : 2017.10.24
  • 심사 : 2018.01.10
  • 발행 : 2018.09.30
⟨ 이전 논문 다음 논문 ⟩

초록

Since Cookson et al. first reported the association of atopy with chromosome 11q13 in 1989, there have been numerous studies of genetics for allergic diseases. Their aim is to identify genetic factors modifying susceptibility to allergic diseases, determining the severity of disease in affected individuals and affecting the response to treatment. With these efforts, allergic diseases can be termed complex genetic disorders, defined as disorders that have numerous contributing genes, each having variable degrees of involvement in any given individual. This review aims to provide information on the current state of genetic research in Korean pediatric allergic diseases.

키워드

참고문헌

  1. Cohen SG, Blumenthal MN. Cooke and Vander Veer on heredity and sensitization. J Allergy Clin Immunol 2002;110:674-80. https://doi.org/10.1016/S0091-6749(02)70054-7
  2. Cookson WO, Sharp PA, Faux JA, Hopkin JM. Linkage between immunoglobulin E responses underlying asthma and rhinitis and chromosome 11q. Lancet 1989;1:1292-5.
  3. Kim KE. Genetics of atopy and asthma. Pediatr Allergy Respir Dis 1999; 9:343-50.
  4. Holloway JW, Prescott SL. The origins of allergic disease. In: O'Hehir RE, Holgate ST, Sheikh A, editors. Middleton's allergy essentials. Philadelphis (PA): Elsvier; 2016. p. 29-50.
  5. Koh YY, Lee MH, Kim CK, Min YG, Kim YK, Min KU, et al. A familial predisposition in bronchial hyperresponsiveness among patients with allergic rhinitis. J Allergy Clin Immunol 1998;102(6 Pt 1):921-6. https://doi.org/10.1016/S0091-6749(98)70329-X
  6. Kim YK, Cho SH, Koh YY, Son JW, Jee YK, Lee MH, et al. Skin reactivity to inhalant allergens, total serum IgE levels, and bronchial responsiveness to methacholine are increased in parents of nonatopic asthmatic children. J Allergy Clin Immunol 1999;104(2 Pt 1):311-6. https://doi.org/10.1016/S0091-6749(99)70372-6
  7. Holloway JW, Yang IA, Holgate ST. Genetics of allergic disease. J Allergy Clin Immunol 2010;125(2 Suppl 2):S81-94. https://doi.org/10.1016/j.jaci.2009.10.071
  8. International HapMap Consortium. A haplotype map of the human genome. Nature 2005;437:1299-320. https://doi.org/10.1038/nature04226
  9. McCarthy MI, Abecasis GR, Cardon LR, Goldstein DB, Little J, Ioannidis JP, et al. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet 2008;9:356-69. https://doi.org/10.1038/nrg2344
  10. Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, Collins FS, et al. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci U S A 2009;106:9362-7. https://doi.org/10.1073/pnas.0903103106
  11. Shin HD, Kim LH, Park BL, Jung JH, Kim JY, Chung IY, et al. Association of eotaxin gene family with asthma and serum total IgE. Hum Mol Genet 2003;12:1279-85. https://doi.org/10.1093/hmg/ddg142
  12. Shin HD, Kim LH, Park BL, Choi YH, Park HS, Hong SJ, et al. Association of interleukin 18 (IL18) polymorphisms with specific IgE levels to mite allergens among asthmatic patients. Allergy 2005;60:900-6. https://doi.org/10.1111/j.1398-9995.2005.00619.x
  13. Chae SC, Park BL, Park CS, Ryu HJ, Yang YS, Lee SO, et al. Putative association of RUNX1 polymorphisms with IgE levels in a Korean population. Exp Mol Med 2006;38:583-8. https://doi.org/10.1038/emm.2006.68
  14. Kim Y, Park CS, Shin HD, Choi JW, Cheong HS, Park BL, et al. A promoter nucleotide variant of the dendritic cell-specific DCNP1 associates with serum IgE levels specific for dust mite allergens among the Korean asthmatics. Genes Immun 2007;8:369-78. https://doi.org/10.1038/sj.gene.6364394
  15. Park HW, Lee JE, Shin ES, Lee JY, Bahn JW, Oh HB, et al. Association between genetic variations of vascular endothelial growth factor receptor 2 and atopy in the Korean population. J Allergy Clin Immunol 2006; 117:774-9. https://doi.org/10.1016/j.jaci.2005.12.1328
  16. Kim HB, Lee YC, Lee SY, Jung J, Jin HS, Kim JH, et al. Gene-gene interaction between IL-13 and IL-13Ralpha1 is associated with total IgE in Korean children with atopic asthma. J Hum Genet 2006;51:1055-62. https://doi.org/10.1007/s10038-006-0061-x
  17. Kim ES, Kim SH, Kim KW, Park HS, Shin ES, Lee JE, et al. Involvement of Fc(epsilon)R1beta gene polymorphisms in susceptibility to atopy in Korean children with asthma. Eur J Pediatr 2009;168:1483-90. https://doi.org/10.1007/s00431-009-0960-x
  18. Sohn MH, Lee JH, Kim KW, Kim SW, Lee SH, Kim KE, et al. Genetic variation in the promoter region of chitinase 3-like 1 is associated with atopy. Am J Respir Crit Care Med 2009;179:449-56. https://doi.org/10.1164/rccm.200809-1422OC
  19. Lee JH, Kim KW, Gee HY, Lee J, Lee KH, Park HS, et al. A synonymous variation in protease-activated receptor-2 is associated with atopy in Korean children. J Allergy Clin Immunol 2011;128:1326-34.e3. https://doi.org/10.1016/j.jaci.2011.06.036
  20. Kim KW, Park J, Lee JH, Lee HS, Lee J, Lee KH, et al. Association of genetic variation in chitotriosidase with atopy in Korean children. Ann Allergy Asthma Immunol 2013;110:444-9.e1. https://doi.org/10.1016/j.anai.2013.03.009
  21. Weidinger S, Gieger C, Rodriguez E, Baurecht H, Mempel M, Klopp N, et al. Genome-wide scan on total serum IgE levels identifies FCER1A as novel susceptibility locus. PLoS Genet 2008;4:e1000166. https://doi.org/10.1371/journal.pgen.1000166
  22. Kim JH, Cheong HS, Park JS, Jang AS, Uh ST, Kim YH, et al. A genome-wide association study of total serum and mite-specific IgEs in asthma patients. PLoS One 2013;8:e71958. https://doi.org/10.1371/journal.pone.0071958
  23. Moffatt MF, Gut IG, Demenais F, Strachan DP, Bouzigon E, Heath S, et al. A large-scale, consortium-based genomewide association study of asthma. N Engl J Med 2010;363:1211-21. https://doi.org/10.1056/NEJMoa0906312
  24. Moffatt MF, Kabesch M, Liang L, Dixon AL, Strachan D, Heath S, et al. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature 2007;448:470-3. https://doi.org/10.1038/nature06014
  25. Kang MJ, Yu HS, Seo JH, Kim HY, Jung YH, Kim YJ, et al. GSDMB/ORMDL3 variants contribute to asthma susceptibility and eosinophil-mediated bronchial hyperresponsiveness. Hum Immunol 2012;73:954-9. https://doi.org/10.1016/j.humimm.2012.06.009
  26. Torgerson DG, Ampleford EJ, Chiu GY, Gauderman WJ, Gignoux CR, Graves PE, et al. Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations. Nat Genet 2011;43:887-92. https://doi.org/10.1038/ng.888
  27. Ferreira MA, Matheson MC, Duffy DL, Marks GB, Hui J, Le Souef P, et al. Identification of IL6R and chromosome 11q13.5 as risk loci for asthma. Lancet 2011;378:1006-14. https://doi.org/10.1016/S0140-6736(11)60874-X
  28. Hirota T, Takahashi A, Kubo M, Tsunoda T, Tomita K, Doi S, et al. Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population. Nat Genet 2011;43:893-6. https://doi.org/10.1038/ng.887
  29. Kim SH, Cho BY, Park CS, Shin ES, Cho EY, Yang EM, et al. Alpha-T-catenin (CTNNA3) gene was identified as a risk variant for toluene diisocyanate-induced asthma by genome-wide association analysis. Clin Exp Allergy 2009;39:203-12. https://doi.org/10.1111/j.1365-2222.2008.03117.x
  30. Kim JH, Park BL, Cheong HS, Bae JS, Park JS, Jang AS, et al. Genome-wide and follow-up studies identify CEP68 gene variants associated with risk of aspirin-intolerant asthma. PLoS One 2010;5:e13818. https://doi.org/10.1371/journal.pone.0013818
  31. Shin SW, Park J, Kim YJ, Uh ST, Choi BW, Kim MK, et al. A highly sensitive and specific genetic marker to diagnose aspirin-exacerbated respiratory disease using a genome-wide association study. DNA Cell Biol 2012;31:1604-9. https://doi.org/10.1089/dna.2012.1688
  32. Park BL, Kim TH, Kim JH, Bae JS, Pasaje CF, Cheong HS, et al. Genome- wide association study of aspirin-exacerbated respiratory disease in a Korean population. Hum Genet 2013;132:313-21. https://doi.org/10.1007/s00439-012-1247-2
  33. Kabesch M, Schedel M, Carr D, Woitsch B, Fritzsch C, Weiland SK, et al. IL-4/IL-13 pathway genetics strongly influence serum IgE levels and childhood asthma. J Allergy Clin Immunol 2006;117:269-74. https://doi.org/10.1016/j.jaci.2005.10.024
  34. Yang IA, Savarimuthu S, Kim ST, Holloway JW, Bell SC, Fong KM. Gene- environmental interaction in asthma. Curr Opin Allergy Clin Immunol 2007;7:75-82. https://doi.org/10.1097/ACI.0b013e328012ce39
  35. Holloway JW, Savarimuthu Francis S, Fong KM, Yang IA. Genomics and the respiratory effects of air pollution exposure. Respirology 2012;17: 590-600. https://doi.org/10.1111/j.1440-1843.2012.02164.x
  36. Bonnelykke K, Sleiman P, Nielsen K, Kreiner-Moller E, Mercader JM, Belgrave D, et al. A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations. Nat Genet 2014;46:51-5. https://doi.org/10.1038/ng.2830
  37. Lee SH, Kang MJ, Yu HS, Hong K, Jung YH, Kim HY, et al. Association between recent acetaminophen use and asthma: modification by polymorphism at TLR4. J Korean Med Sci 2014;29:662-8. https://doi.org/10.3346/jkms.2014.29.5.662
  38. Kang SH, Jung YH, Kim HY, Seo JH, Lee JY, Kwon JW, et al. Effect of paracetamol use on the modification of the development of asthma by reactive oxygen species genes. Ann Allergy Asthma Immunol 2013;110: 364-9.e1. https://doi.org/10.1016/j.anai.2013.03.008
  39. Zhang Y, Moffatt MF, Cookson WO. Genetic and genomic approaches to asthma: new insights for the origins. Curr Opin Pulm Med 2012;18:6-13. https://doi.org/10.1097/MCP.0b013e32834dc532
  40. Kim TH, An SH, Cha JY, Shin EK, Lee JY, Yoon SH, et al. Association of 5-hydroxytryptamine (serotonin) receptor 4 (5-HTR4) gene polymorphisms with asthma. Respirology 2011;16:630-8. https://doi.org/10.1111/j.1440-1843.2011.01963.x
  41. Lee SH, Chang HS, Jang AS, Park SW, Park JS, Uh ST, et al. The association of a single-nucleotide polymorphism of the IL-2 inducible T-cell Kinase gene with asthma. Ann Hum Genet 2011;75:359-69. https://doi.org/10.1111/j.1469-1809.2010.00637.x
  42. Kim JH, Cheong HS, Park BL, Bae JS, Jung S, Yoon SH, et al. A new association between polymorphisms of the SLC6A7 gene in the chromosome 5q31-32 region and asthma. J Hum Genet 2010;55:358-65. https://doi.org/10.1038/jhg.2010.34
  43. Oh SH, Park SM, Lee YH, Cha JY, Lee JY, Shin EK, et al. Association of peroxisome proliferator-activated receptor-gamma gene polymorphisms with the development of asthma. Respir Med 2009;103:1020-4. https://doi.org/10.1016/j.rmed.2009.01.015
  44. Jung JS, Park BL, Cheong HS, Bae JS, Kim JH, Chang HS, et al. Association of IL-17RB gene polymorphism with asthma. Chest 2009;135:1173-80. https://doi.org/10.1378/chest.08-1595
  45. Cheong HS, Kim LH, Park BL, Choi YH, Park HS, Hong SJ, et al. Association analysis of interleukin 5 receptor alpha subunit (IL5RA) polymorphisms and asthma. J Hum Genet 2005;50:628-34. https://doi.org/10.1007/s10038-005-0304-2
  46. Shin HD, Park BL, Kim LH, Jung JH, Wang HJ, Kim YJ, et al. Association of tumor necrosis factor polymorphisms with asthma and serum total IgE. Hum Mol Genet 2004;13:397-403. https://doi.org/10.1093/hmg/ddh036
  47. Lee SG, Kim BS, Kim JH, Lee SY, Choi SO, Shim JY, et al. Gene-gene interaction between interleukin-4 and interleukin-4 receptor alpha in Korean children with asthma. Clin Exp Allergy 2004;34:1202-8. https://doi.org/10.1111/j.1365-2222.2004.02015.x
  48. Sohn MH, Kim SH, Kim KW, Jee HM, Park HS, Kim KE. RANTES gene promoter polymorphisms are associated with bronchial hyperresponsiveness in Korean children with asthma. Lung 2008;186:37-43. https://doi.org/10.1007/s00408-007-9049-3
  49. Sohn MH, Kim SH, Song TW, Kim KW, Kim ES, Park HS, et al. Cytotoxic T lymphocyte-associated antigen-4 gene polymorphisms confer susceptibility to atopic asthma in Korean children. Pediatr Pulmonol 2007;42:542-7. https://doi.org/10.1002/ppul.20622
  50. Kim YK, Park HW, Yang JS, Oh SY, Chang YS, Shin ES, et al. Association and functional relevance of E237G, a polymorphism of the high-affinity immunoglobulin E-receptor beta chain gene, to airway hyper-responsiveness. Clin Exp Allergy 2007;37:592-8. https://doi.org/10.1111/j.1365-2222.2007.02680.x
  51. Kim YK, Oh HB, Lee EY, Gho YS, Lee JE, Kim YY. Association between a genetic variation of CC chemokine receptor-2 and atopic asthma. Allergy 2007;62:208-9.
  52. Kim HK, Jang TW, Jung MH, Park HW, Lee JE, Shin ES, et al. Association between genetic variations of the transforming growth factor $\beta$ receptor type III and asthma in a Korean population. Exp Mol Med 2010; 42:420-7. https://doi.org/10.3858/emm.2010.42.6.043
  53. Du R, Litonjua AA, Tantisira KG, Lasky-Su J, Sunyaev SR, Klanderman BJ, et al. Genome-wide association study reveals class I MHC-restricted T cell-associated molecule gene (CRTAM) variants interact with vitamin D levels to affect asthma exacerbations. J Allergy Clin Immunol 2012; 129:368-73, 373.e1-5. https://doi.org/10.1016/j.jaci.2011.09.034
  54. Canova C, Dunster C, Kelly FJ, Minelli C, Shah PL, Caneja C, et al. PM10- induced hospital admissions for asthma and chronic obstructive pulmonary disease: the modifying effect of individual characteristics. Epidemiology 2012;23:607-15. https://doi.org/10.1097/EDE.0b013e3182572563
  55. Jongepier H, Boezen HM, Dijkstra A, Howard TD, Vonk JM, Koppelman GH, et al. Polymorphisms of the ADAM33 gene are associated with accelerated lung function decline in asthma. Clin Exp Allergy 2004;34: 757-60. https://doi.org/10.1111/j.1365-2222.2004.1938.x
  56. Lee SH, Jang AS, Woo Park S, Park JS, Kim YK, Uh ST, et al. Genetic effect of single-nucleotide polymorphisms in the PPARGC1B gene on airway hyperreactivity in asthmatic patients. Clin Exp Allergy 2011;41:1533- 44. https://doi.org/10.1111/j.1365-2222.2011.03801.x
  57. Lee JH, Park HS, Park SW, Jang AS, Uh ST, Rhim T, et al. ADAM33 polymorphism: association with bronchial hyper-responsiveness in Korean asthmatics. Clin Exp Allergy 2004;34:860-5. https://doi.org/10.1111/j.1365-2222.2004.01977.x
  58. Kim KW, Lee KE, Hong JY, Kim MN, Heo WI, Sohn MH, et al. Involvement of IL-10 gene promoter polymorphisms in the susceptibility for childhood asthma. Lung 2011;189:417-23. https://doi.org/10.1007/s00408-011-9312-5
  59. Park HW, Lee JE, Kim SH, Kim YK, Min KU, Kim YY, et al. Genetic variation of IL13 as a risk factor of reduced lung function in children and adolescents: a cross-sectional population-based study in Korea. Respir Med 2009;103:284-8. https://doi.org/10.1016/j.rmed.2008.08.009
  60. Hong SJ, Lee SY, Kim HB, Kim JH, Kim BS, Choi SO, et al. IL-5 and thromboxane A2 receptor gene polymorphisms are associated with decreased pulmonary function in Korean children with atopic asthma. J Allergy Clin Immunol 2005;115:758-63. https://doi.org/10.1016/j.jaci.2004.10.047
  61. Gerrard JW, Vickers P, Gerrard CD. The familial incidence of allergic disease. Ann Allergy 1976;36:10-5.
  62. Namkung JH, Lee JE, Kim E, Cho HJ, Kim S, Shin ES, et al. IL-5 and IL-5 receptor alpha polymorphisms are associated with atopic dermatitis in Koreans. Allergy 2007;62:934-42. https://doi.org/10.1111/j.1398-9995.2007.01445.x
  63. Namkung JH, Lee JE, Kim E, Park GT, Yang HS, Jang HY, et al. An association between IL-9 and IL-9 receptor gene polymorphisms and atopic dermatitis in a Korean population. J Dermatol Sci 2011;62:16-21.
  64. Namkung JH, Lee JE, Kim E, Kim S, Kim S, Shin ES, et al. Association of single nucleotide polymorphisms in the IL-12 (IL-12A and B) and IL-12 receptor (IL-12Rbeta1 and beta2) genes and gene-gene interactions with atopic dermatitis in Koreans. J Dermatol Sci 2010;57:199-206. https://doi.org/10.1016/j.jdermsci.2009.12.003
  65. Namkung JH, Lee JE, Kim E, Kim HJ, Seo EY, Jang HY, et al. Association of polymorphisms in genes encoding IL-4, IL-13 and their receptors with atopic dermatitis in a Korean population. Exp Dermatol 2011; 20:915-9. https://doi.org/10.1111/j.1600-0625.2011.01357.x
  66. Kim E, Lee JE, Namkung JH, Park JH, Kim S, Shin ES, et al. Association of the single-nucleotide polymorphism and haplotype of the interleukin 18 gene with atopic dermatitis in Koreans. Clin Exp Allergy 2007;37: 865-71. https://doi.org/10.1111/j.1365-2222.2007.02717.x
  67. Lee HJ, Ha SJ, Han H, Kim JW. Distribution of HLA-A, B alleles and polymorphisms of TAP and LMP genes in Korean patients with atopic dermatitis. Clin Exp Allergy 2001;31:1867-74. https://doi.org/10.1046/j.1365-2222.2001.01042.x
  68. Kim E, Lee JE, Namkung JH, Kim PS, Kim S, Shin ES, et al. Single nucleotide polymorphisms and the haplotype in the DEFB1 gene are associated with atopic dermatitis in a Korean population. J Dermatol Sci 2009; 54:25-30. https://doi.org/10.1016/j.jdermsci.2008.12.005
  69. Namkung JH, Lee JE, Kim E, Byun JY, Kim S, Shin ES, et al. Hint for association of single nucleotide polymorphisms and haplotype in SPINK5 gene with atopic dermatitis in Koreans. Exp Dermatol 2010;19:1048-53. https://doi.org/10.1111/j.1600-0625.2010.01142.x
  70. Cho HR, Uhm YK, Kim HJ, Ban JY, Chung JH, Yim SV, et al. Glutathione S-transferase M1 (GSTM1) polymorphism is associated with atopic dermatitis susceptibility in a Korean population. Int J Immunogenet 2011;38:145-50. https://doi.org/10.1111/j.1744-313X.2010.00987.x
  71. Lee HS, Kim SH, Kim KW, Baek JY, Park HS, Lee KE, et al. Involvement of human histamine N-methyltransferase gene polymorphisms in susceptibility to atopic dermatitis in korean children. Allergy Asthma Immunol Res 2012;4:31-6. https://doi.org/10.4168/aair.2012.4.1.31
  72. Namkung JH, Lee JE, Kim E, Huh IS, Park T, Shin ES, et al. Single nucleotide polymorphism in the FLT4 gene is associated with atopic dermatitis in Koreans. Cytokine 2013;62:110-4. https://doi.org/10.1016/j.cyto.2013.02.006
  73. Kim JS, Choi J, Hahn HJ, Lee YB, Yu DS, Kim JW. Association of macrophage migration inhibitory factor polymorphisms with total plasma IgE levels in patients with atopic dermatitis in Korea. PLoS One 2016;11: e0162477. https://doi.org/10.1371/journal.pone.0162477
  74. Kim JS, Lee SY, Hahn HJ, Lee YB, Yu DS, Kim JW. Association of single-nucleotide polymorphisms of the MBL2 with atopic dermatitis in Korean patients. Ann Dermatol 2017;29:571-7. https://doi.org/10.5021/ad.2017.29.5.571
  75. Sohn MH, Song JS, Kim KW, Kim ES, Kim KE, Lee JM. Association of interleukin-10 gene promoter polymorphism in children with atopic dermatitis. J Pediatr 2007;150:106-8. https://doi.org/10.1016/j.jpeds.2006.08.065
  76. Chung J, Oh SY, Shin YK. Association of glutathione-S-transferase polymorphisms with atopic dermatitis risk in preschool age children. Clin Chem Lab Med 2009;47:1475-81.
  77. Heo WI, Park KY, Jin T, Lee MK, Kim M, Choi EH, et al. Identification of novel candidate variants including COL6A6 polymorphisms in early-onset atopic dermatitis using whole-exome sequencing. BMC Med Genet 2017;18:8.
  78. Irvine AD, McLean WH, Leung DY. Filaggrin mutations associated with skin and allergic diseases. N Engl J Med 2011;365:1315-27. https://doi.org/10.1056/NEJMra1011040
  79. Smith FJ, Irvine AD, Terron-Kwiatkowski A, Sandilands A, Campbell LE, Zhao Y, et al. Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nat Genet 2006;38:337-42. https://doi.org/10.1038/ng1743
  80. Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP, et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 2006;38:441-6. https://doi.org/10.1038/ng1767
  81. Fallon PG, Sasaki T, Sandilands A, Campbell LE, Saunders SP, Mangan NE, et al. A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming. Nat Genet 2009;41: 602-8. https://doi.org/10.1038/ng.358
  82. Yu HS, Kang MJ, Jung YH, Kim HY, Seo JH, Kim YJ, et al. Mutations in the filaggrin are predisposing factor in Korean children with atopic dermatitis. Allergy Asthma Immunol Res 2013;5:211-5. https://doi.org/10.4168/aair.2013.5.4.211
  83. Kim SY, Yang SW, Kim HL, Kim SH, Kim SJ, Park SM, et al. Association between P478S polymorphism of the filaggrin gene & atopic dermatitis. Indian J Med Res 2013;138:922-7.
  84. Park KY, Park MK, Seok J, Li K, Seo SJ. Clinical characteristics of Korean patients with filaggrin-related atopic dermatitis. Clin Exp Dermatol 2016; 41:595-600. https://doi.org/10.1111/ced.12854
  85. Soderhall C, Marenholz I, Kerscher T, Ruschendorf F, Esparza-Gordillo J, Worm M, et al. Variants in a novel epidermal collagen gene (COL29A1) are associated with atopic dermatitis. PLoS Biol 2007;5:e242. https://doi.org/10.1371/journal.pbio.0050242
  86. Sun LD, Xiao FL, Li Y, Zhou WM, Tang HY, Tang XF, et al. Genome-wide association study identifies two new susceptibility loci for atopic dermatitis in the Chinese Han population. Nat Genet 2011;43:690-4. https://doi.org/10.1038/ng.851
  87. Paternoster L, Standl M, Chen CM, Ramasamy A, Bonnelykke K, Duijts L, et al. Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nat Genet 2011;44:187-92.
  88. Kim KW, Myers RA, Lee JH, Igartua C, Lee KE, Kim YH, et al. Genome-wide association study of recalcitrant atopic dermatitis in Korean children. J Allergy Clin Immunol 2015;136:678-84.e4. https://doi.org/10.1016/j.jaci.2015.03.030
  89. Ramasamy A, Curjuric I, Coin LJ, Kumar A, McArdle WL, Imboden M, et al. A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order. J Allergy Clin Immunol 2011;128:996-1005. https://doi.org/10.1016/j.jaci.2011.08.030
  90. Andiappan AK, Wang de Y, Anantharaman R, Parate PN, Suri BK, Low HQ, et al. Genome-wide association study for atopy and allergic rhinitis in a Singapore Chinese population. PLoS One 2011;6:e19719. https://doi.org/10.1371/journal.pone.0019719
  91. Bunyavanich S, Shargorodsky J, Celedon JC. A meta-analysis of Th2 pathway genetic variants and risk for allergic rhinitis. Pediatr Allergy Immunol 2011;22:378-87. https://doi.org/10.1111/j.1399-3038.2010.01124.x
  92. Kim JJ, Min JY, Lee JH. Polymorphisms in the IL-13 and IL-4 receptor alpha genes and allergic rhinitis. Eur Arch Otorhinolaryngol 2007;264: 395-9. https://doi.org/10.1007/s00405-006-0204-x
  93. Lee HM, Park SA, Chung SW, Woo JS, Chae SW, Lee SH, et al. Interleukin-18/-607 gene polymorphism in allergic rhinitis. Int J Pediatr Otorhinolaryngol 2006;70:1085-8. https://doi.org/10.1016/j.ijporl.2005.11.006
  94. Chae SC, Park YR, Li CS, Lee JH, Yang YS, Zhang Q, et al. Analysis of the variations in IL-28RA gene and their association with allergic rhinitis. Exp Mol Med 2006;38:302-9. https://doi.org/10.1038/emm.2006.36
  95. Kim JJ, Lee JH, Jang CH, Kim YS, Chae SC, Chung HT, et al. Chemokine RANTES promoter polymorphisms in allergic rhinitis. Laryngoscope 2004;114:666-9. https://doi.org/10.1097/00005537-200404000-00013
  96. Chae SC, Park YR, Oh GJ, Lee JH, Chung HT. The suggestive association of eotaxin-2 and eotaxin-3 gene polymorphisms in Korean population with allergic rhinitis. Immunogenetics 2005;56:760-4. https://doi.org/10.1007/s00251-004-0746-2
  97. Chae SC, Park YR, Lee YC, Lee JH, Chung HT. The association of TIM-3 gene polymorphism with atopic disease in Korean population. Hum Immunol 2004;65:1427-31. https://doi.org/10.1016/j.humimm.2004.07.002
  98. Li CS, Chae SC, Lee JH, Zhang Q, Chung HT. Identification of single nucleotide polymorphisms in FOXJ1 and their association with allergic rhinitis. J Hum Genet 2006;51:292-7. https://doi.org/10.1007/s10038-006-0359-8
  99. Kim KR, Cho SH, Choi SJ, Jeong JH, Lee SH, Park CW, et al. TAP1 and TAP2 gene polymorphisms in Korean patients with allergic rhinitis. J Korean Med Sci 2007;22:825-31. https://doi.org/10.3346/jkms.2007.22.5.825
  100. Kang I, An XH, Oh YK, Lee SH, Jung HM, Chae SC, et al. Identification of polymorphisms in the RNase3 gene and the association with allergic rhinitis. Eur Arch Otorhinolaryngol 2010;267:391-5. https://doi.org/10.1007/s00405-009-1103-8
  101. Kang I, Oh YK, Lee SH, Jung HM, Chae SC, Lee JH. Identification of polymorphisms in the Toll-like receptor gene and the association with allergic rhinitis. Eur Arch Otorhinolaryngol 2010;267:385-9. https://doi.org/10.1007/s00405-009-1100-y
  102. Kim WK, Kwon JW, Seo JH, Kim HY, Yu J, Kim BJ, et al. Interaction between IL13 genotype and environmental factors in the risk for allergic rhinitis in Korean children. J Allergy Clin Immunol 2012;130:421-6.e5. https://doi.org/10.1016/j.jaci.2012.04.052
  103. Seo JH, Kim HY, Jung YH, Lee E, Yang SI, Yu HS, et al. Interactions between innate immunity genes and early-life risk factors in allergic rhinitis. Allergy Asthma Immunol Res 2015;7:241-8. https://doi.org/10.4168/aair.2015.7.3.241
  104. Taylor DR, Hancox RJ, McRae W, Cowan JO, Flannery EM, McLachlan CR, et al. The influence of polymorphism at position 16 of the beta2-adrenoceptor on the development of tolerance to beta-agonist. J Asthma 2000;37:691-700. https://doi.org/10.3109/02770900009087308
  105. Portelli M, Sayers I. Genetic basis for personalized medicine in asthma. Expert Rev Respir Med 2012;6:223-36. https://doi.org/10.1586/ers.12.9
  106. Cho SH, Oh SY, Bahn JW, Choi JY, Chang YS, Kim YK, et al. Association between bronchodilating response to short-acting beta-agonist and non-synonymous single-nucleotide polymorphisms of beta-adrenoceptor gene. Clin Exp Allergy 2005;35:1162-7. https://doi.org/10.1111/j.1365-2222.2005.02319.x
  107. Kim MH, Kim SH, Kim YK, Hong SJ, Min KU, Cho SH, et al. A polymorphism in the histone deacetylase 1 gene is associated with the response to corticosteroids in asthmatics. Korean J Intern Med 2013;28: 708-14. https://doi.org/10.3904/kjim.2013.28.6.708
  108. Kim JH, Lee SY, Kim HB, Jin HS, Yu JH, Kim BJ, et al. TBXA2R gene polymorphism and responsiveness to leukotriene receptor antagonist in children with asthma. Clin Exp Allergy 2008;38:51-9.
  109. Lockett GA, Patil VK, Soto-Ramirez N, Ziyab AH, Holloway JW, Karmaus W. Epigenomics and allergic disease. Epigenomics 2013;5:685-99. https://doi.org/10.2217/epi.13.68
  110. Kim YJ, Park SW, Kim TH, Park JS, Cheong HS, Shin HD, et al. Genome- wide methylation profiling of the bronchial mucosa of asthmatics: relationship to atopy. BMC Med Genet 2013;14:39.
  111. Eder W, Ege MJ, von Mutius E. The asthma epidemic. N Engl J Med 2006; 355:2226-35. https://doi.org/10.1056/NEJMra054308