Association of CD14 promoter polymorphisms and soluble CD14 levels in mite allergen sensitization of children in Taiwan

Abstract

CD14 is responsible for environmental lipopolysaccharide recognition and is a positional candidate gene for allergy. We hypothesized that genetic polymorphisms in the promoter region of the CD14 gene may be associated with Dermatophagoides pteronysinnus (Der p) allergen sensitization in children. Three single nucleotide polymorphisms (SNPs) of the CD14 promoter region, C(À159)T, A(À1,145)G, and G(À1,359)T were genotyped, and analyzed in 240 randomized casecontrol school-age children in Taiwan. Serum concentrations of IgE and soluble CD14 (sCD14) were also assayed. We found a significant inverse correlation of sCD14 and total serum IgE levels in our study population. Moreover, sCD14 binds Der p allergen in vitro in a dose-dependent manner. The distribution of three SNPs genotypes was similar in asthmatic children and the control group. However, there was a significant difference in the distribution of genotype CD14 G(À1,359)T, but not C(À159)T, between mite-sensitive and non-sensitive children. Haplotype analysis showed strong linkage disequilibrium among these three SNPs in the CD14 promoter region. Carriers of the CD14À159C/À1,145A/À1,359T haplotype had the highest IgE and lowest sCD14 levels as compared to other haplotypes. Our results support the hypothesis that CD14 gene variants may play an important role in influencing allergen sensitization of children in Taiwan.

Soluble CD14 and total IgE in the serum of atopic and nonatopic adolescents in relation to environmental factors: a pilot study / Topivi receptor CD14 i ukupni IgE u serumu mladih atopičara odrasle dobi u ovisnosti o čimbenicima iz okoliša: pilot istraživanje

“…Lower serum sCD14 levels in atopic adolescents found in our study corroborate reports from Sweden and Taiwan, which showed that atopic children had significantly lower serum sCD14 than non-atopic children (6,11). In contrast, other studies reported higher serum sCD14 levels in allergic alveolitis (12), atopic dermatitis (13), and asthma (14,15,20).…”

“…The level of specific IgE in serum is a good marker of sensitisation but not of clinically symptomatic allergy, and new markers of atopic diseases have been investigated (3). One such potential marker is the cluster of differentiation 14 (CD14), a multifunctional receptor on the macrophages, monocytes, and dendritic cells that binds lipopolysaccharides (LPS) and other bacterial wall compounds, fungal wall components (β-glucan, mannans), and indoor allergens (dust mite and cockroach allergens) (4)(5)(6)(7). In serum it takes soluble form (sCD14), and its concentrations have been associated with serum IgE and asthma (8).…”

“…As sCD14 levels seem to vary with age, sex, and genetic variants (9), its clinical relevance as a possible marker of atopic diseases is still not clear. Recent studies in children and adults reported apparently contradictory results; some have associated lower serum sCD14 with atopy (10) or sensitisation to house dust mites (6), and some reported increased sCD14 levels in various allergic diseases such as allergic alveolitis and atopic dermatitis (11)(12)(13)(14). These contradicting effects of sCD14 can be explained by the fact that higher sCD14 levels in asthmatic patients are secondary to allergic inflammation.…”

Polymorphisms of the CD14 gene and atopic phenotypes in Czech patients with IgE-mediated allergy

“…The results of previous studies indicate that the CD14 gene plays an important role in the determination of sensitisation to environmental allergens as well as in innate immunity against pathogens (Tan et al 2006). The results of association studies of the CD14 gene with atopic phenotype in our populations confirm the importance of not only promoter, but also exon polymorphisms in the CD14 gene in modulating expression and severity of the atopic diseases.…”

“…at positions -1,619, -1,359, -1,145, -809, and -550) were characterised in the promoter of the gene encoding CD14. Vercelli et al (2001b) and Tan et al (2006) showed that carriers of the -1359T/-1145A/ -159C haplotype had the highest levels of IgE, and the lowest levels of sCD14, and conversely carriers of the 1359G/-1145G/-159T haplotype had the highest levels of sCD14 and the lowest IgE values. According to Martin et al (2006), during acute asthma, plasma sCD14 levels were higher, but increases were only in subjects with CD14 -159TT and -159CT, and not in those with -159CC.…”