Abstract
Our understanding of the complex genetic susceptibility to occupational contact dermatitis (OCD) is still in the early stage. The search for candidate susceptibility genes focused mainly on proteins involved in skin barrier and immune response which have a key role in both irritant and allergic contact dermatitis (respectively, ICD and ACD). Furthermore, for ACD genetic variations in enzymes involved in metabolism of contact allergens have been investigated. Among skin barrier genes, loss-of-function mutations in the filaggrin gene (FLG) have been identified as a risk factor for irritant contact dermatitis (ICD); the risk-modifying effect of FLG mutations was stronger in the presence of atopic dermatitis. In ACD, the impact of FLG mutations was allergen specific and dependent on the outcome measure and the exposure pattern. Several studies reported association of genetic polymorphisms in the metabolizing enzymes N-acetyltransferase and glutathione S-transferase with ACD; however the results are so far inconclusive. Among inflammatory genes, there appears to be an effect of TNF gene polymorphisms on susceptibility to both irritant and allergic CD, suggesting that they share some common pathways.
At present, the predictive value of genetic markers for the appearance of OCD is too low for reasonable identification of susceptible individuals in occupational health practice.
Further well-designed studies in larger cohorts with a well-defined disease phenotype and external exposure in the control as well as in the case group are needed to confirm and extend our knowledge of the impact of genetic variations on the susceptibility to OCD.
Similar content being viewed by others
References
Allen MH, Wakelin SH, Holloway D, Lisby S, Baadsgaard O, Barker JNWN, McFadden JP (2000) Association of TNFA gene polymorphism at position-308 with susceptibility to irritant contact dermatitis. Immunogenetics 51:201–205
Belsito DV (2005) Occupational contact dermatitis: etiology, prevalence, and resultant impairment/disability. J Am Acad Dermatol 53:303–313
Blömeke B, Brans R, Dickel H, Bruckner T, Erdmann S, Heesen M, Merk HF, Coenraads PJ (2009a) Association between TNFA-308G/a polymorphism and sensitization to para-phenylenediamine: a case-control study. Allergy 64:279–283
Blömeke B, Brans R, Coenraads PJ, Dickel H, Bruckner T, Hein DW, Heesen M, Merk HF, Kawakubo Y (2009b) Para-phenylenediamine and allergic sensitization: risk modification by N-acetyltransferase 1 and 2 genotypes. Br J Dermatol 161:1130–1135
Bolt HM, Thier R (2006) Relevance of the deletion polymorphisms of the glutathione S-transferases GSTT1 and GSTM1 in pharmacology and toxicology. Curr Drug Metab 7:613–628
Brans R, Dickel H, Bruckner T, Coenraads PJ, Heesen M, Merk HF, Blomeke B (2005) MnSOD polymorphisms in sensitized patients with delayed-type hypersensitivity reactions to the chemical allergen para-phenylene diamine: a case-control study. Toxicology 212:148–154
Brown SJ, Cordell HJ (2008) Are filaggrin mutations associated with hand eczema or contact allergy?–we do not know. Br J Dermatol 158:1383–1384
de Cid R, Riveira-Munoz E, Zeeuwen PL, Robarge J, Liao W, Dannhauser EN, Giardina E, Stuart PE, Nair R, Helms C, Escaramís G, Ballana E, Martín-Ezquerra G, den Heijer M, Kamsteeg M, Joosten I, Eichler EE, Lázaro C, Pujol RM, Armengol L, Abecasis G, Elder JT, Novelli G, Armour JA, Kwok PY, Bowcock A, Schalkwijk J, Estivill X (2009) Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis. Nat Genet 41:211–215
Colagiovanni A, Di Renzo L, Sarlo F, Schiavino D, De Lorenzo A (2016) Role of TNF-alpha polymorphism in patients with nickel allergy: a marker of susceptibility to contact polysensitization. Eur Rev Med Pharmacol Sci 20:2663–2666
Diepgen TL, Kanerva L (2006) Occupational skin diseases. Eur J Dermatol 16:324–330
Elias PM, Schmuth M (2009) Abnormal skin barrier in the etiopathogenesis of atopic dermatitis. Curr Allergy Asthma Rep 9:265–272
English JS (2004) Current concepts of irritant contact dermatitis. Occup Environ Med 61:722–726
Ertam I, Itirli G, Onay H, Alper S, Ozkinay F (2009) Interleukin-1 receptor antagonist and tumour necrosis factor-alpha gene polymorphisms in Turkish patients with allergic contact dermatitis. Contact Dermatitis 61:86–90
Esser PR, Martin SF (2017) Pathomechanisms of contact sensitization. Curr Allergy Asthma Rep 17:83
Fluhr JW, Darlenski R, Angelova-Fischer I, Tsankov N, Basketter D (2008) Skin irritation and sensitization: mechanisms and new approaches for risk assessment. 1. Skin irritation. Skin Pharmacol Physiol 21:124–135
Friedmann PS, Sanchez-Elsner T, Schnuch A (2015) Genetic factors in susceptibility to contact sensitivity. Contact Dermatitis 72:263–274
de Jongh CM, Khrenova L, Verberk MM, Calkoen F, van Dijk FJ, Voss H, John SM, Kezic S (2008a) Loss-of-function polymorphisms in the filaggrin gene are associated with an increased susceptibility to chronic irritant contact dermatitis: a case-control study. Br J Dermatol 159:621–627
de Jongh CM, John SM, Bruynzeel DP, Calkoen F, van Dijk FJ, Khrenova L, Rustemeyer T, Verberk MM, Kezic S (2008b) Cytokine gene polymorphisms and susceptibility to chronic irritant contact dermatitis. Contact Dermatitis 58:269–277
de Jongh CM, Khrenova L, Kezic S, Rustemeyer T, Verberk MM, John SM (2008c) Polymorphisms in the interleukin-1 gene influence the stratum corneum interleukin-1alpha concentration in uninvolved skin of patients with chronic irritant contact dermatitis. Contact Dermatitis 58:263–268
Kezic S, Jakasa I (2016) Filaggrin and skin barrier function. Curr Probl Dermato 49:1–7
Kimber I, Basketter DA, Gerberick GF, Dearman RJ (2002) Allergic contact dermatitis. Int Immunopharmacol 2:201–211
Koppes SA, Engebretsen KA, Agner T, Angelova-Fischer I, Berents T, Brandner J, Brans R, Clausen ML, Hummler E, Jakasa I, Jurakić-Tončic R, John SM, Khnykin D, Molin S, Holm JO, Suomela S, Thierse HJ, Kezic S, Martin SF, Thyssen JP (2017) Current knowledge on biomarkers for contact sensitization and allergic contact dermatitis. Contact Dermatitis 77:1–16
Landeck L, Visser M, Kezic S, John SM (2012a) Impact of tumour necrosis factor-α polymorphisms on irritant contact dermatitis. Contact Dermatitis 66:221–227
Landeck L, Visser M, Skudlik C, Brans R, Kezic S, John SM (2012b) Clinical course of occupational irritant contact dermatitis of the hands in relation to filaggrin genotype status and atopy. Br J Dermatol 167:1302–1309
Landeck L, Visser M, Kezic S, John SM (2013) IL1A-889 C/T gene polymorphism in irritant contact dermatitis. J Eur Acad Dermatol Venereol 27:1040–1043
Landeck L, Visser M, Skudlik C, Brans R, Kezic S, John SM (2014) No remarkable differences in rates of sensitization to common type I and IV allergens between FLG loss-of-function mutation carriers and wild-type subjects. Contact Dermatitis 70:27–34
Lerbaek A, Bisgaard H, Agner T, Ohm Kyvik K, Palmer CN, Menné T (2007) Filaggrin null alleles are not associated with hand eczema or contact allergy. Br J Dermatol 157:1199–1204
Molin S, Vollmer S, Weiss EH, Ruzicka T, Prinz JC (2009) Filaggrin mutations may confer susceptibility to chronic hand eczema characterized by combined allergic and irritant contact dermatitis. Br J Dermatol 161:801–807
Molin S, Vollmer S, Weiss EH, Weisenseel P, Ruzicka T, Prinz JC (2011) Deletion of the late cornified envelope genes LCE3B and LCE3C may promote chronic hand eczema with allergic contact dermatitis. J Investig Allergol Clin Immunol 21:472–479
Nacak M, Erbagci Z, Aynacioglu AS (2006) Human arylamine N-acetyltransferase 2 polymorphism and susceptibility to allergic contact dermatitis. Int J Dermatol 45:323–326
Najim RA, Al-waizt M, Al-Razzuqi RA (2005) Acetylator phenotype in Iraqi patients with allergic contact dermatitis. Ann Saudi Med 25:473–476
Novak N, Baurecht H, Schafer T, Rodriguez E, Wagenpfeil S, Klopp N, Heinrich J, Behrendt H, Ring J, Wichmann E, Illig T, Weidinger S (2008) Loss-of-function mutations in the filaggrin gene and allergic contact sensitization to nickel. J Invest Dermatol 128:1430–1435
Pastore S, Mascia F, Mariotti F, Dattilo C, Girolomoni G (2004) Chemokine networks in inflammatory skin diseases. Eur J Dermatol 14:203–208
Pot LM, Alizadeh BZ, Ahrenberg D, Coenraads PJ, Snieder H, Blömeke B (2011) No major role for glutathione S-transferase gene polymorphisms in sensitization to para-phenylenediamine and other xenobiotics: a study of association and a meta-analysis. Br J Dermatol 164:890–892
Proksch E, Brandner JM, Jensen JM (2008) The skin – an indispensable barrier. Exp Dermatol 17:1063–1072
Reich K, Westphal G, Konig IR, Mossner R, Kruger U, Ziegler A, Neumann C, Schnuch A (2003) Association of allergic contact dermatitis with a promoter polymorphism in the IL16 gene. J Allergy Clin Immunol 112:1191–1194
Ross-Hansen K, Linneberg A, Johansen JD, Hersoug LG, Brasch-Andersen C, Menné T, Thyssen JP (2013) The role of glutathione S-transferase and claudin-1 gene polymorphisms in contact sensitization: a cross-sectional study. Br J Dermatol 168:762–770
Schnuch A, Westphal G, Mössner R, Uter W, Reich K (2011) Genetic factors in contact allergy--review and future goals. Contact Dermatitis 64:2–23
Thyssen JP, Kezic S (2014) Causes of epidermal filaggrin reduction and their role in the pathogenesis of atopic dermatitis. J Allergy Clin Immunol 134:792–799
Thyssen JP, Johansen JD, Linneberg A, Menné T, Nielsen NH, Meldgaard M, Szecsi PB, Stender S, Carlsen BC (2010) The association between null mutations in the filaggrin gene and contact sensitization to nickel and other chemicals in the general population. Br J Dermatol 162:1278–1285
Timmerman JG, Heederik D, Spee T, van Rooy FG, Krop EJ, Koppelman GH, Rustemeyer T, Smit LA (2016) Contact dermatitis in the construction industry: the role of filaggrin loss-of-function mutations. Br J Dermatol 174:348–355
Visser MJ, Landeck L, Campbell LE, McLean WHI, Weidinger S, Calkoen F, John SM, Kezic S (2013) Impact of atopic dermatitis and loss-of-function mutations in the filaggrin gene on the development of occupational irritant contact dermatitis. Br J Dermatol 168:326–332
Visser MJ, Verberk MM, Campbell LE, McLean WH, Calkoen F, Bakker JG, van Dijk FJ, Bos JD, Kezic S (2014) Filaggrin loss-of-function mutations and atopic dermatitis as risk factors for hand eczema in apprentice nurses: part II of a prospective cohort study. Contact Dermatitis 70:139–150
Wang BJ, Shiao JS, Chen CJ, Lee YC, Guo YL (2007) Tumour necrotizing factor-alpha promoter and GST-T1 genotype predict skin allergy to chromate in cement workers in Taiwan. Contact Dermatitis 57:309–315
Weidinger S, Novak N (2016) Atopic dermatitis. Lancet 387:1109–1122
Westphal GA, Reich K, Schulz TG, Neumann C, Hallier E, Schnuch A (2000a) N-acetyltransferase 1 and 2 polymorphisms in para-substituted arylamine-induced contact allergy. Br J Dermatol 142:1121–1127
Westphal GA, Schnuch A, Schulz TG, Reich K, Aberer W, Brasch J, Koch P, Wessbecher R, Szliska C, Bauer A, Hallier E (2000b) Homozygous gene deletions of the glutathione S-transferases M1 and T1 are associated with thimerosal sensitization. Int Arch Occup Environ Health 73:384–388
Westphal GA, Schnuch A, Moessner R, Konig IR, Kranke B, Hallier E, Ziegler A, Reich K (2003) Cytokine gene polymorphisms in allergic contact dermatitis. Contact Dermatitis 48:93–98
Westphal GA, Rihs HP, Schaffranek A, Zeiler T, Werfel T, Heratizadeh A, Dickel H, Weisshaar E, Bauer A, Schliemann S, Reich K, Breuer K, Schröder-Kraft C, Worm M, Molin S, Brans R, Schäkel K, Schwantes H, Pföhler C, Szliska C, Kreft B, Löffler H, Bünger J, Brüning T, Geier J, Schnuch A (2016) A variant of the CXCL11 gene may influence susceptibility to contact allergy, particularly in polysensitized patients. Contact Dermatitis 75:303–307
Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW (1997) Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci U S A 94:3195–3199
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this entry
Cite this entry
Kezic, S. (2018). Genetic Identification of Individuals with Increased Risk of Developing Occupational Skin Diseases. In: John, S., Johansen, J., Rustemeyer, T., Elsner, P., Maibach, H. (eds) Kanerva’s Occupational Dermatology. Springer, Cham. https://doi.org/10.1007/978-3-319-40221-5_107-2
Download citation
DOI: https://doi.org/10.1007/978-3-319-40221-5_107-2
Received:
Accepted:
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-40221-5
Online ISBN: 978-3-319-40221-5
eBook Packages: Springer Reference MedicineReference Module Medicine