Archives of Dermatological Research

, Volume 304, Issue 10, pp 787–793 | Cite as

Interactions between FLG mutations and allergens in atopic dermatitis

Original Paper

Abstract

Filaggrin gene (FLG) mutations and sensitization in patients with atopic dermatitis (AD) have been well documented. However, whether an interaction exists between these mutations and specific sensitization in AD patients is still unknown. The aim of the study was to explore the interaction between FLG mutations and specific sensitization in AD patients. A total of 249 AD outpatients were recruited in the current study. Skin prick tests were conducted to assess the patient’s sensitization to specific allergens. FLG mutations were analyzed through comprehensive sequencing. Logistic regression analyses were conducted to determine the interactions between FLG mutations and sensitization present. The mean age of the patients was 3.5 years, and the mean age of onset of AD was 9.6 months. The mean SCORAD of the patients was 25.8. Fourteen types of mutations were identified in the FLG of 64 patients. A total of 24 (9.6 %) and 29 (11.6 %) cases were mutated with 3321delA and K4671X, respectively. Sensitization to at least one type of allergen was detected in 118 patients (47.4 %). Logistic regression analyses showed that FLG mutations presented an interaction with sensitization to peanut and did not interact with the other detected allergens among AD patients. Sensitization to peanut allergens would have an interaction with the mutation of K4671X and the combined mutations in FLG in patients with atopic dermatitis. However, sensitization to the other common allergens might not interact with FLG mutations in the development of atopic dermatitis.

Keywords

Atopic dermatitis Filaggrin gene Mutations Sensitization Allergen 

References

  1. 1.
    Abramovits W (2005) Atopic dermatitis. J Am Acad Dermatol 53:S86–S93PubMedCrossRefGoogle Scholar
  2. 2.
    Ben-Shoshan M, Kagan RS, Alizadehfar R et al (2009) Is the prevalence of peanut allergy increasing? A 5-year follow-up study in children in Montreal. J Allergy Clin Immunol 123:783–788PubMedCrossRefGoogle Scholar
  3. 3.
    Bisgaard H, Simpson A, Palmer CN et al (2008) Gene–environment interaction in the onset of eczema in infancy: filaggrin loss-of-function mutations enhanced by neonatal cat exposure. PLoS Med 5:e131PubMedCrossRefGoogle Scholar
  4. 4.
    Brown SJ, Asai Y, Cordell HJ et al (2011) Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy. J Allergy Clin Immunol 127:661–667PubMedCrossRefGoogle Scholar
  5. 5.
    Brown SJ, McLean WH (2009) Eczema genetics: current state of knowledge and future goals. J Invest Dermatol 129:543–552PubMedCrossRefGoogle Scholar
  6. 6.
    Chen H, Common JE, Haines RL et al (2011) Wide spectrum of filaggrin-null mutations in atopic dermatitis highlights differences between Singaporean Chinese and European populations. Br J Dermatol 165:106–114PubMedCrossRefGoogle Scholar
  7. 7.
    Chung BY, Kim HO, Park CW, Lee CH (2010) Diagnostic usefulness of the serum-specific IgE, the skin prick test and the atopy patch test compared with that of the oral food challenge test. Ann Dermatol 22:404–411PubMedCrossRefGoogle Scholar
  8. 8.
    Dai YS (2007) Allergens in atopic dermatitis. Clin Rev Allergy Immunol 33:157–166PubMedCrossRefGoogle Scholar
  9. 9.
    Eigenmann PA, Sicherer SH, Borkowski TA, Cohen BA, Sampson HA (1998) Prevalence of IgE-mediated food allergy among children with atopic dermatitis. Pediatrics 101:E8PubMedCrossRefGoogle Scholar
  10. 10.
    Enomoto H, Hirata K, Otsuka K et al (2008) Filaggrin null mutations are associated with atopic dermatitis and elevated levels of IgE in the Japanese population: a family and case–control study. J Hum Genet 53:615–621PubMedCrossRefGoogle Scholar
  11. 11.
    Fallon PG, Sasaki T, Sandilands A et al (2009) A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming. Nat Genet 41:602–608PubMedCrossRefGoogle Scholar
  12. 12.
    Hamajima N, Yuasa H, Matsuo K, Kurobe Y (1999) Detection of gene–environment interaction by case-only studies. Jpn J Clin Oncol 29:490–493PubMedCrossRefGoogle Scholar
  13. 13.
    Han Y, Chung SJ, Kim J, Ahn K, Lee SI (2009) High sensitization rate to food allergens in breastfed infants with atopic dermatitis. Ann Allergy Asthma Immunol 103:332–336PubMedCrossRefGoogle Scholar
  14. 14.
    Hanifin JM, Rajka G (1980) Diagnostic features of atopic eczema. Acta Dermatol Venereol (Stockh) 92:44–47Google Scholar
  15. 15.
    Hoffjan S, Parwez Q, Petrasch-Parwez E, Falkenstein D, Nothnagel M, Epplen JT (2006) Association screen for atopic dermatitis candidate gene regions using microsatellite markers in pooled DNA samples. Int J Immunogenet 33:401–409PubMedCrossRefGoogle Scholar
  16. 16.
    Hubiche T, Ged C, Benard A et al (2007) Analysis of SPINK 5, KLK 7 and FLG genotypes in a French atopic dermatitis cohort. Acta Derm Venereol 87:499–505PubMedCrossRefGoogle Scholar
  17. 17.
    Hudson TJ (2006) Skin barrier function and allergic risk. Nat Genet 38:399–400PubMedCrossRefGoogle Scholar
  18. 18.
    Jacobsen HP, Herskind AM, Nielsen BW, Husby S (2001) IgE in unselected like-sexed monozygotic and dizygotic twins at birth and at 6 to 9 years of age: high but dissimilar genetic influence on IgE levels. J Allergy Clin Immunol 107:659–663PubMedCrossRefGoogle Scholar
  19. 19.
    Lack G, Fox D, Northstone K, Golding J (2003) Factors associated with the development of peanut allergy in childhood. N Engl J Med 348:977–985PubMedCrossRefGoogle Scholar
  20. 20.
    Li M, Chen X, Chen R, Bao Y, Yao Z (2011) Filaggrin gene mutations are associated with independent atopic asthma in Chinese patients. Allergy 66:1616–1617PubMedCrossRefGoogle Scholar
  21. 21.
    Li M, Liu Q, Liu J et al (2012) Mutations analysis in filaggrin gene in northern China patients with atopic dermatitis. J Eur Acad Dermatol Venereol. doi:10.1111/j.1468-3083.2011.04435.x Google Scholar
  22. 22.
    Liu AH, Jaramillo R, Sicherer SH et al (2010) National prevalence and risk factors for food allergy and relationship to asthma: results from the National Health and Nutrition Examination Survey 2005–2006. J Allergy Clin Immunol 126(798–806):e713Google Scholar
  23. 23.
    Ma L, Zhang L, Di ZH et al (2010) Association analysis of filaggrin gene mutations and atopic dermatitis in Northern China. Br J Dermatol 162:225–227PubMedCrossRefGoogle Scholar
  24. 24.
    Nemoto-Hasebe I, Akiyama M, Nomura T, Sandilands A, McLean WH, Shimizu H (2009) Clinical severity correlates with impaired barrier in filaggrin-related eczema. J Invest Dermatol 129:682–689PubMedCrossRefGoogle Scholar
  25. 25.
    Nemoto-Hasebe I, Akiyama M, Nomura T, Sandilands A, McLean WH, Shimizu H (2009) FLG mutation p.Lys4021X in the C-terminal imperfect filaggrin repeat in Japanese patients with atopic eczema. Br J Dermatol 161:1387–1390PubMedCrossRefGoogle Scholar
  26. 26.
    Niggemann B, Sielaff B, Beyer K, Binder C, Wahn U (1999) Outcome of double-blind, placebo-controlled food challenge tests in 107 children with atopic dermatitis. Clin Exp Allergy 29:91–96PubMedCrossRefGoogle Scholar
  27. 27.
    Ong PY, Ferdman RM, Church JA (2010) Late-onset of IgE sensitization to microbial allergens in young children with atopic dermatitis. Br J Dermatol 162:159–161PubMedCrossRefGoogle Scholar
  28. 28.
    Ott H, Stanzel S, Ocklenburg C, Merk HF, Baron JM, Lehmann S (2009) Total serum IgE as a parameter to differentiate between intrinsic and extrinsic atopic dermatitis in children. Acta Derm Venereol 89:257–261PubMedCrossRefGoogle Scholar
  29. 29.
    Palmer CN, Irvine AD, Terron-Kwiatkowski A et al (2006) Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 38:441–446PubMedCrossRefGoogle Scholar
  30. 30.
    Patel T, Gawkrodger DJ (2011) Food allergy in patients with eczema: immediate symptoms are usual, with nuts and tomatoes the major allergens. J Eur Acad Dermatol Venereol 25:865–867PubMedCrossRefGoogle Scholar
  31. 31.
    Sandilands A, O’Regan GM, Liao H et al (2006) Prevalent and rare mutations in the gene encoding filaggrin cause ichthyosis vulgaris and predispose individuals to atopic dermatitis. J Invest Dermatol 126:1770–1775PubMedCrossRefGoogle Scholar
  32. 32.
    Sandilands A, Terron-Kwiatkowski A, Hull PR et al (2007) Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema. Nat Genet 39:650–654PubMedCrossRefGoogle Scholar
  33. 33.
    Schuttelaar ML, Kerkhof M, Jonkman MF et al (2009) Filaggrin mutations in the onset of eczema, sensitization, asthma, hay fever and the interaction with cat exposure. Allergy 64:1758–1765PubMedCrossRefGoogle Scholar
  34. 34.
    Shek LP, Cabrera-Morales EA, Soh SE, et al. (2010) A population-based questionnaire survey on the prevalence of peanut, tree nut, and shellfish allergy in 2 Asian populations. J Allergy Clin Immunol 126:324–331, 331 e321–e327Google Scholar
  35. 35.
    Venter C, Hasan Arshad S, Grundy J et al (2010) Time trends in the prevalence of peanut allergy: three cohorts of children from the same geographical location in the UK. Allergy 65:103–108PubMedCrossRefGoogle Scholar
  36. 36.
    Werfel T, Breuer K (2004) Role of food allergy in atopic dermatitis. Curr Opin Allergy Clin Immunol 4:379–385PubMedCrossRefGoogle Scholar
  37. 37.
    Zhang H, Guo Y, Wang W, Shi M, Chen X, Yao Z (2011) Mutations in the filaggrin gene in Han Chinese patients with atopic dermatitis. Allergy 66:420–427PubMedCrossRefGoogle Scholar
  38. 38.
    Zhang H, Guo Y, Wang W, Yu X, Yao Z (2011) Associations of FLG mutations between ichthyosis vulgaris and atopic dermatitis in Han Chinese. Allergy 66:1253–1254PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  1. 1.Department of Dermatology, Xinhua HospitalShanghai Jiaotong University School of MedicineShanghaiChina
  2. 2.Department of DermatologyBao’an Maternal and Child Health HospitalShenzhenChina
  3. 3.Department of DermatologyShanxi Provincial Children’s HospitalTaiyuanChina
  4. 4.Central Laboratory, Bao’an Maternal and Child Health HospitalShenzhenChina

Personalised recommendations