A (G→C) transversion in the 3′ UTR of the human ECP (eosinophil cationic protein) gene correlates to the cellular content of ECP

Abstract

Eosinophil cationic protein (ECP) is a cytotoxic protein produced by and secreted from human eosinophil granulocytes. ECP may be involved in the injury of epithelial cells in allergic diseases such as asthma. The objectives were to determine the prevalence of the ECP gene polymorphism 562(G > C) in apparently healthy subjects and subjects with allergy and relate the prevalence to clinical disease and to serum and cellular levels of ECP. The 562(G > C) ECP gene polymorphism was determined by gene sequencing of the ECP gene from DNA prepared from 163 apparently healthy subjects and 151 subjects with allergic and nonallergic asthma or other diseases. ECP was measured by a sensitive radioimmunoassay. A polymorphism was detected at position 562, which mapped to the 3' untranslated region (UTR) of the gene encoding the ECP (RNase 3). Sixty-nine percent of the population had the 562GG genotype and 4%, the 562CC genotype. The cellular content of ECP in peripheral blood eosinophil granulocytes was significantly lower in cells from subjects with the 562GC (4.6+/-1.5 microg/10(6) eosinophils) and 562CC (3.2+/-0.7 microg/10(6) eosinophils) genotypes as compared with those with the 562GG genotype (6.0+/-1.9 microg/10(6) eosinophils; P < 0.001). A close link was found to the 434(G > C) ECP gene polymorphism. Associations between the 562(G > C) polymorphism or haplotypes of the two polymorphisms to allergy were not found. The 562(G > C) polymorphism in the 3'-end of the UTR of the ECP gene may determine the ECP content in human eosinophils, but unlike the 434(G > C) polymorphism, the 562(G > C) polymorphism is not related to allergy.

The Coding ECP 434(G&gt;C) Gene Polymorphism Determines the Cytotoxicity of ECP but Has Minor Effects on Fibroblast-Mediated Gel Contraction and No Effect on RNase Activity

“…Several SNPs have been identified in the human ECP gene (16) and some have been linked to function or cellular content of ECP. In a study by Jönsson et al the 562(GϾC) polymorphism in the 3ЈUTR region of the ECP gene correlated to the cellular levels of ECP (17). In another study the intron polymorphism Ϫ38(CϾA) that is positioned in a putative GATA-1 binding site was correlated to serum ECP levels (18).…”

Eosinophil Cationic Protein: Overview of Biological and Genetic Features

“…A close relationship between the 562(G > C) polymorphism, located in the 3'-untranslated region of RNASE3, and the 434(G > C) polymorphism was established by Jonsson et al (2006). The authors observed that the 434GG genotype and the 562GG genotype were only present together, and that the cellular content of ECP in peripheral blood eosinophils was lower in cells that were taken from subjects with the 562GC or 562CC genotypes.…”

“…The ECP gene 434(G > C) polymorphism and variant alleles of the polymorphic gene have been associated with different pathological conditions ( Jonsson et al, 2002( Jonsson et al, , 2006Eriksson et al, 2007aEriksson et al, , 2007bTrulson et al, 2007). Subjects that were allergic had a significantly higher prevalence of the homozygous 434G genotype, and no subjects that had allergic symptoms were homozygous for the 434C genotype, suggesting that this polymorphism is related to the development of allergic symptoms in asthma ( Jonsson et al, 2002).…”

Eosinophil catonic protein – current concepts and controversies

“…The in tra cel lu lar con cen tra tion of ECP was sig ni fi can tly lower in eosi nop hil gra nu lo ci tes from sub jec ts wi th ECP 562CC ge no type but a re la tion ship has not been des cri bed be tween the 562(G>C) po lymor phi sm and al ler gy (29). The po ten tial re la tion ship between the 3'-untranslated re gion and expres sion of mR NA ha ve been des cri bed in ot her ge nes (30).…”