Association study using combination analysis of SNP and STRP markers: CD14 promoter polymorphism and IgE level in Taiwanese asthma children

Abstract

Chromosome 5, especially the 5q31-33 region, may contain one or more loci to control total serum IgE as well as asthma and bronchial hyperresponsiveness. To investigate the regions related with IgE level in chromosome 5, we performed a case-control association study on 105 high-IgE-level and 85 normal-IgE-level asthmatic children using 43 microsatellite markers that span the whole chromosome 5 with 5 cM intervals. One of microsatellite marker, D5S2011, had significantly different allele frequency between the two asthmatic groups. E allele (143 bp) of the D5S2011 marker was more frequent in high-IgE asthmatics. CD14 is the candidate gene of atopy and asthma and is distant from D5S2011 by about 1 Mb. We analyzed the SNP genotypes in the CD14 gene region alone and in combination with microsatellite marker D5S2011. The CD14/À2984 polymorphism but not the CD14/À159 is associated with IgE level in Taiwanese asthmatic children. The CD14/À159 allele was observed only to be associated with IgE level when À159T was part of a haplotype containing a D5S2011 E allele. The combination analysis using SNP and STRP markers provided a novel method for increasing detection power in candidate gene association studies.

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

“…These conflicting results suggest that CD14/À159 and the putative susceptibility variant are in the same LD block in some study subjects but not in all populations. In our previous report, we also found that CD14/À159 was associated with IgE levels only when the À159T allele was part of a haplotype containing a specific D5S2011 allele (D5S2011, 143 bp) but not other D5S2011 alleles (Wang et al 2005a). Another possible explanation for inconsistent results from different studies is that association with IgE level should be a specific haplotype (Baldini et al 2000;Vercelli et al 2001b) or combination of genotypes (Vercelli et al 2001a).…”

“…Previously, we found that CD14 gene promoter polymorphism was associated with IgE levels in Taiwanese asthmatic children (Wang et al 2005a). In this study, we hypothesized that CD14 may recognize aeroallergens, such as dust mites, and influence postnatal switching of the T helper cell response.…”

The role of Toll-like receptors and related receptors of the innate immune system in asthma

“…Geneenvironment interaction unique to specific populations may explain the difference in results compared with previous studies. Alternatively, linkage disequilibrium is likely to be important, as indicated by a study from Taiwan showing an association of the CD14 -2984 polymorphism, rather than -159, with serum IgE levels [36].…”

Racial differences in the association of CD14 polymorphisms with serum total IgE levels and allergen skin test reactivity

“…Many studies found a similar association of the CD14/-159 T allele with lower IgE levels among subjects that were British,20 French,24 Australian children,21 Czech,23 and Chinese 29. However, no association of the CD14/-159 locus was observed in Polish children,31 two German populations,32,33 Taiwanese children with asthma,36 two Japanese cohorts20,37 and a general population in Barbados of African descent 34,35. Conversely, the CD14-159T allele was found to be over transmitted to atopic subjects in an inbred population of Hutterites,38 new mothers living in the Detroit urban area,56 Caucasians living in the St Paul (MN, USA) urban area,39 Tunisian children,41 and among atopic Australian white adults 40.…”

“…Recent studies have suggested that CD14 polymorphisms and haplotype markers are associated with allergic disease and interact with environmental exposures to affect the development of atopy. Wang et al36 reported that, among Taiwanese children with asthma, the CD14/−159 SNP was only associated with total IgE levels when the T allele was part of a haplotype containing a specific D5S2011 E allele (143 bp). Ober et al38 reported that the CD14-159T allele was over-transmitted to atopic Hutterites only when the allele was on a haplotype with the D5S642 marker allele (D5S642, 185-bp) but not those with other D5S642 markers.…”