Association of a chromosome 1q21 locus in close proximity to a late cornified envelope-like proline-rich 1 (LELP1) gene with total serum IgE levels

Abstract

The chromosomal region 1q21 has been linked to atopic dermatitis in previous studies. Seven polymorphic repeats were identified in a 0.5 Mb region of chromosome 1q21 encompassing a small prolinerich protein (SPRR) gene cluster, a few S100 gene family members, loricin, and several uncharacterized genes. These repeats were genotyped by fragment length polymorphism analysis in 133 atopic case-parent trios, of which 111 probands had atopic asthma. Our trio-based analysis for association with atopy and atopic asthma revealed no significant allelic or genotypic association for any of the seven loci tested. However, a significant association was observed with locus 5 (3.65 Mb of contig NT_032962) and log 10 serum IgE levels (F = 3.93, P = 0.0008). Results were also replicated in an independent case-control cohort (N p = 165, N c = 166), where a significant association with log 10 serum IgE levels was observed in the patient group (P = 0.0005). Interestingly, locus 5 is 6.2 kb upstream of a late cornified envelope-like proline-rich 1 (LELP1) gene which encodes a novel small proline rich protein. Further, we have also found a significant association of rs7534334 (tagged SNP from LELP1) SNP with log 10 serum IgE levels in the patient group (P = 0.0029). Thus, our results identify a chromosomal region in close proximity to a novel gene and highlight the need for intense research on LELP1 and other genes close by with respect to atopic disorders.

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

“…Some authors [35], have found an association of this chromosome 1q21 tagged single nucleotide polymorphism (SNPs) within the LELP1 gene [rs7534334] with serum IgE levels. These results pointed to the need for research on LELP1 and other genes on EDC that could be related with many inflammatory diseases of the skin like AD and psoriasis.…”

“…Other authors [35], refer a correlation of log10 serum IgE levels and rs7534334 in a group of asthmatic patients being the mutant genotype (TT) in patients, those with higher levels of IgE comparing with controls (TT) and comparing with wild type genotype (CC) in patients (3.49 ± 0.91 vs 2.43 ± 0.52 vs 2.92 ± 0.59) .This point to the works who showed that when skin barrier function is compromised even without skin disease there is an increased incidence of atopic disease [28].…”

“…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).The molecular basis for the skin barrier deficiency could be a secondary phenomenon associated with the epidermal differentiation complex (EDC) and barrier candidate genes like FLG ( filaggrin) and LELP1 (late cornified envelope-like proline-rich 1) as we found in our results.Other authors [35], refer a correlation of log10 serum IgE levels and rs7534334 in a group of asthmatic patients being the mutant genotype (TT) in patients, those with higher levels of IgE comparing with controls (TT) and comparing with wild type genotype (CC) in patients (3.49 ± 0.91 vs 2.43 ± 0.52 vs 2.92 ± 0.59) .This point to the works who …”

“…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].…”

Role of genetic aspect in pathogenesis of atopic dermatitis

“…This gene encodes a late cornified envelopelike prolin-rich protein. Indian scientists found a significant link between rs7534334 SNP and log10 serum IgE levels in the group of patients (Sharma et al 2007). However, this was only a single study and the authors stressed the need for further research.…”