Lelp-1, Its Role in Atopic Dermatitis and Asthma: Poland and Portugal

Abstract

Background: Atopic dermatitis (AD) that begins in childhood and is the first step of the so-called 'atopic march'. The chromosome 1q21 region has been associated with AD and psoriasis, with a peak in Epidermal Differentiation Complex (EDC) in a region of 2.05 Mb. The aim of this work was to study LELP-1 (late cornified envelope-like proline-rich 1) polymorphism [rs7534334] located within the EDC, in AD and asthma in two European populations: Portugal and Poland. Methods:We studied 110 individuals in the control group and 129 asthmatics in the Portuguese cohort; 100 controls and 45 patients with AD and asthma in the Poland cohort. Written informed consent was obtained from all participating individuals. LELP-1 genotypes were determined by the PCR-RFLP technique. All statistical analyses were carried out using SPSS 21.0 software. Results:The results were considered statistically significant with p<0.05. We found that the CC genotype was more frequent in Poland's cohort with AD and asthma when compared with controls (p=0.004), (OR: 2.80 [1. 34-5.82]; adjusted p=0.006) and the C allele was also a risk factor (OR: 2.40 [1. 35-4.28]; adjusted p=0.003) to both diseases in this group. When compared the cohort from Portugal with Poland, there was a trend for TT genotype to be a risk for asthma in the Portuguese cohort (OR=7. 49 [0.92-60.91], adjusted p=0.06). C allele was more frequent in the cohort from Poland and T allele, in the cohort from Portugal (p=0.047).Conclusion: These findings demonstrate that genetic variation of skin barrier genes like LELP-1 might contribute to allergic diseases. The upregulated genes in lesional epidermal transcriptome consisted of proliferation-related, EDC, inflammatory antimicrobial genes and the upregulated genes dermal transcriptome included T-cell activation, IL-2 receptor α, Th2-related, Th22, Th17-related and collagen genes [24,25]. Lelp-1, Its Role in Atopic DermatitisStudies of association of genes in AD put in evidence the cluster of the EDC [7,23] and other barrier candidates [29], but the most important associations were related to FLG (filaggrin) [13,[30][31][32] and two null mutations (R510X and 2282del4) [33,34]. In this study we have studied the role of LELP1 (another EDC gene) polymorphism (late cornified envelope-like proline-rich 1) [rs7534334] (a polymorphism 258 bp downstream of the LELP1) using the HapMap database (HapMap data rel28 Phase II+III, August 10, NCBI B36 assembly) and its association with atopic dermatitis and asthma in a Portuguese and Poland's cohort.LELP1 codes for a SPRR (cornifin) family protein, [35] assuming that many of those proteins (FLG, SPRR, loricrin, involucrin) are stored and released from keratohyalin granules in the granular layer .The cell membrane is then, covered with cross-linked intercellular proteins forming the cornified envelope [2,6,36,37]. Transglutaminases crosslink intercellular proteins and also link lipids to the cornified envelope, forming also the lipid envelope to provide a water barrier function [37].The chromos...