Clinical features of children with atopic dermatitis according to filaggrin gene variants

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Arghavan Ziaali
Laleh Sharifi
Shahram Teimourian
Bita Hasani
Anna Isaian
Mansoureh Shariat


Atopic Dermatitis, AD, Filaggrin, FLG, single nucleotide polymorphism, SNP, Iran


Background: Filament aggregating protein (Filaggrin) is a skeletal cell component that provides a protective function for the epidermis. Mutations of the filaggrin gene (FLG) cause a loss of filaggrin protein. These mutations are seen in 50% of atopic dermatitis (AD). The aim of the study was to investigate the polymorphisms and mutations of the FLG in Iranian children
with AD.
Materials and methods: This project was a case-controlled study with 25 children diagnosed with AD as the case group and 25 healthy children as the control group. Demographic data, clinical manifestations, and filaggrin single nucleotide polymorphisms (SNPs) and mutations were recorded. Blood samples were collected for the immunoglobulin E (IgE) assay and complete blood count tests.
Results: We found a significant association between the presence of polymorphism (rs66831674) and patients’ age, and polymorphism (rs41267154) and early onset of AD. We found no significant differences between the FLG polymorphisms with respect to the severity of AD, ethnicity, concurrent allergic diseases, eosinophilia, and IgE serum levels.
Conclusion: Interestingly, FLG variants (rs66831674 and rs41267154) were associated with age and early onset of AD. However, additional studies are required to confirm these results on a large scale of Iranian population. Moreover, establishing a cohort prospective study is suggested to assess the progression of other atopic disorders based on FLG polymorphisms.

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1. Akdis CA, Akdis M, Bieber T, Bindslev-Jensen C, Boguniewicz M, Eigenmann P, et al. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy,
Asthma and Immunology/PRACTALL Consensus Report. J Allergy Clin Immunol. 2006;118(1):152–69.
2. Kliegman RM, Behrman RE, Jenson HB, Stanton BM. Nelson textbook of pediatrics e-book. Cambridge, MA: Elsevier; 2007.
3. Kim J, Kim BE, Leung DYM. Pathophysiology of atopic dermatitis: Clinical implications. Allergy Asthma Proc. 2019;40(2):84-92.
4. Stefanovic N, Flohr C, Irvine AD. The exposome in atopic dermatitis. Allergy. 2020;75(1):63–74.
5. Boothe WD, Tarbox JA, Tarbox MB. Atopic dermatitis: Pathophysiology. Fortson E, Feldman S, Strowd L (eds.), In: Management of atopic dermatitis. Dordrecht, the Netherlands: Springer; 2017, pp. 21–37.
6. O’Regan GM, Sandilands A, McLean WI, Irvine AD. Filaggrin in atopic dermatitis. J Allergy Clin Immunol. 2008;122(4):689–93.
7. Irvine AD, McLean WI, Leung DY. Filaggrin mutations associated with skin and allergic diseases. New England J Med. 2011;365(14):1315–27.
8. van den Oord RA, Sheikh A. Filaggrin gene defects and risk of developing allergic sensitisation and allergic disorders:
Systematic review and meta-analysis. BMJ. 2009;339:b2433.
9. Mohamed N, Hashad D. Filaggrin gene polymorphisms in Egyptian atopic dermatitis patients. J Med Res Inst. 2010;31(1):19–23.
10. Khaledi M, Fotouhi A, Farhadi E, Mahdaviani B, Sotoudeh S, Tavakoli M, et al. Filaggrin single nucleotide polymorphisms in atopic dermatitis. Acta Dermatovenerol Croat. 2014;22(3):200–4.
11. Hassani B, Isaian A, Shariat M, Mollanoori H, Sotoudeh S, Babaei V, et al. Filaggrin gene polymorphisms in Iranian ichthyosis vulgaris and atopic dermatitis patients. Int J Dermatol. 2018;57(12):1485–91.
12. McAleer MA, Irvine AD. The multifunctional role of filaggrin in allergic skin disease. J Allergy Clin Immunol. 2013;131(2):280–91.
13. Paller AS, Spergel JM, Mina-Osorio P, Irvine AD. The atopic march and atopic multimorbidity: Many trajectories, many
pathways. J Allergy Clin Immunol. 2019;143(1):46–55.
14. Brough HA, Liu AH, Sicherer S, Makinson K, Douiri A, Brown SJ, et al. Atopic dermatitis increases the effect of exposure to
peanut antigen in dust on peanut sensitization and likely peanut allergy. J Allergy Clin Immunol. 2015;135(1):164–70, e4.
15. Rupnik H, Rijavec M, Korošec P. Filaggrin loss‐of‐function mutations are not associated with atopic dermatitis that
develops in late childhood or adulthood. Br J Dermatol. 2015;172(2):455–61.
16. Soares P, Fidler K, Felton J, Tavendale R, Hövels A, Bremner S, et al. Individuals with filaggrin‐related eczema and asthma have increased long‐term medication and hospital admission costs. Br J Dermatol. 2018;179(3):717–23.;
17. Heede NG, Thyssen JP, Thuesen BH, Linneberg A, Szecsi PB, Stender S, et al. Health‐related quality of life in adult dermatitis patients stratified by filaggrin genotype. Contact Dermat. 2017;76(3):167–77.
18. Tokura Y. Extrinsic and intrinsic atopic dermatitis. Katayama I, Murota H, Satoh T (Eds.), In: Evolution of atopic dermatitis in the 21st century. Dordrecht, the Netherlands: Springer; 2018, pp. 181–99.
19. Morar N, Cookson WOCM, Harper JI, Moffatt MF. Filaggrin mutations in children with severe atopic dermatitis. J Invest
Dermatol. 2007;127(7):1667–72.
20. Kabashima-Kubo R, Nakamura M, Sakabe J-i, Sugita K, Hino R, Mori T, et al. A group of atopic dermatitis without IgE elevation or barrier impairment shows a high Th1 frequency: Possible immunological state of the intrinsic type. J Dermatol Sci. 2012;67(1):37–43. jdermsci.2012.04.004
21. Fuchs E, Raghavan S. Getting under the skin of epidermal morphogenesis. Nat Rev Genet. 2002;3(3):199–209.
22. Akiyama M. FLG mutations in ichthyosis vulgaris and atopic eczema: Spectrum of mutations and population genetics. Br J Dermatol. 2010;162(3):472–7.
23. Ghaderi R, Tabiee S, Peyrovi S, Jafari Pour M. Prevalence of atopic dermatitis and its risk factors in 2–5 years old children
at kindergartens of Birjand city (2008). J Birjand Univ Med Sci. 2012;19(3):286–93.