Background: It is assumed that beside alterations in the filaggrin gene (FLG), disturbances within genes encoding other cornified envelope proteins are also involved in atopic dermatitis (AD). To identify new potential markers of AD, we studied the polymorphisms of genes encoding repetin (RPTN), cornulin (CRNN), and their expression in the skin of AD patients. Methods: Polymorphisms in CRNN (rs941934), RPTN (rs284544, rs28441202, rs3001978, and rs12117644), and FLG mutations (R2447X, S3247X) were analyzed by TaqMan genotyping assay and by PCR-RFLP in the blood samples of 159 AD patients and 108 healthy subjects. The expression levels of CRNN and RPTN were determined by qRT-PCR in 34 AD skin samples (17 lesional and 17 nonlesional) and in 27 skin biopsies from healthy volunteers. The AD patients were recruited from the clinic of the university hospital between 2012 and 2014. Results:CRNN rs941934 (A allele) was associated with AD (OR 2.095, p = 0.008), a severe course of disease (p = 0.041), elevated IgE levels (p = 0.047), eosinophilia (p = 0.018), and concomitant asthma (p = 0.004). The mRNA level of CRNN was decreased in the AD skin (p = 0.041). In the AD patients without FLG mutations, the CC genotype of RPTN rs3001978 was associated with AD (OR 0.39, p = 0.037), early age at onset (p = 0.033), pruritus (p = 0.021), severity of AD (p = 0.045), and concomitant asthma (p = 0.041). The elevated mRNA levels of RPTN in lesional (p p = 0.017) AD skin were observed. Conclusions: The single-nucleotide polymorphisms of CRNN (rs941934) and RPTN (rs3001978, rs28441202) may contribute to AD development, but further studies on a larger group of AD patients are needed to verify this assumption.
Int Arch Allergy Immunol 2017;172:11-19
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