Changes in the expression of cornified envelope (CE) proteins are thought to affect the development and course of atopic dermatitis (AD). The aim of this study was to examine the expression level of CE proteins in order to identify new molecular markers of the AD phenotype. Expression levels of CE proteins were evaluated in the skin of patients with AD (38 biopsies) and healthy subjects (26 biopsies). Levels of FLG, FLG2 and SPRR3 mRNAs and proteins were reduced in AD skin. Levels of LELP-1 and SPRR1A transcripts and proteins were significantly increased in AD skin. SPRR3v2 mRNA level in non-lesional AD skin correlated with severity of AD, and SPRR3 protein level in non-lesional AD skin correlated inversely with pruritus. FLG protein level in AD skin correlated inversely with severity of AD. These results point to SPRR3 as an important factor in AD and itch.
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 < 0.001) and nonlesional (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.
There is some evidence that genes involved in the pathogenesis of atopic dermatitis, in addition to the filaggrin (FLG) gene, may be located at chromosome region 1q21. The aim of this study was to examine the association of single nucleotide polymorphisms in the region of the late cornified envelope-like proline-rich 1 (LELP1), hornerin (HRNR) and FLG genes with the course and risk of atopic dermatitis. Single nucleotide polymorphisms and mutations were genotyped by PCR restriction fragment length polymorphism and real-time PCR in a group of 152 patients with atopic dermatitis and 104 healthy volunteers. CC genotype and C-allele of LELP1 rs7534334 were found in patients with atopic dermatitis and were associated with elevated levels of serum immunoglobulin E, severity of atopic dermatitis and concomitant asthma. LELP1 rs7534334 enhanced the risk of atopic dermatitis nearly 2.5-fold. This pilot study suggests that rs7534334 SNP, located in the LELP1 region, may be a potential genetic marker for the risk and course of atopic dermatitis.
Evaluation of CAV1 expression offers valuable prognostic information for patients with colorectal cancer, and could be used to select patients with stage I or II disease, who are at increased risk of unfavorable outcomes.
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