Coexistence of 2282del4 FLG gene mutation and IL-18 –137G/C gene polymorphism enhances the risk of atopic dermatitis

Introduction Atopic dermatitis (AD) pathogenesis appears in the context of the correlation between cornified envelope proteins and immunological factors. Aim To estimate the association between FLG R501X and 2282del4 gene mutations, –137 G/C IL-18 and –1112 C/T IL-13 gene polymorphisms and their influence on AD course and the risk in the Polish population. Material and methods One hundred and fifty-two AD patients and 123 healthy volunteers were included into the study. Amplification refractory mutation system – polymerase chain reaction method was used. Results 2282del4 FLG mutation, predominant (p = 0.04) in Polish AD patients, enhanced the risk of AD (OR = 2.35; p = 0.01) and was associated with itch (p = 0.023). GG genotype of IL-18 was prevailing in AD (p < 0.0001), associated with elevated IgE levels (p = 0.00074) and pruritus (p < 0.0001). GG genotype and G-allele in –137 position of IL-18 increased AD risk (OR = 5.4; p = 0.0001, respectively, o‎r = 5.3; p = 0.000029). –1112 C/T polymorphism of IL-13 was associated with elevated IgE levels (p = 0.00049), pruritus (p = 0.0005), SCORAD score (p = 0.02), concomitant asthma (p = 0.0087) and AD risk (OR = 2.02; p = 0.012). Coexistence of 2282del4 or R501X FLG gene mutation with GG genotype of IL-18 was associated with a 6-fold higher risk of AD (OR = 5.8; p = 0.00013), contrary to combined occurrence of FLG mutations with T-allele in –1112 position of IL-13 gene (OR = 0.12; p = 0.1). Conclusions 2282del4 FLG mutation similarly to GG genotype and G-allele in –137 position of IL-18 gene enhance the risk of AD in the Polish population. Coexistence of FLG mutations with GG genotype of IL-18 may be helpful to estimate chances of AD development.