Article

Polymorphisms in the 5 ' region of the CD14 gene are associated with eczema in young children

Harvard University, Cambridge, Massachusetts, United States
Journal of Allergy and Clinical Immunology (Impact Factor: 11.25). 06/2005; 115(5):1056-62. DOI: 10.1016/j.jaci.2005.02.006
Source: PubMed

ABSTRACT Variants in the CD14 gene (CD14) are hypothesized to be associated with atopic disorders. However, most studies have only investigated one polymorphism in this gene.
We sought to study the association of 5 single nucleotide polymorphisms (SNPs) in the 5' flanking region of CD14 with eczema and serum IgE levels in young children.
We genotyped 5 SNPs in an approximately 6.5-kb region in the 5' region of CD14 in 344 2-year-old white children from 2 birth cohorts in the northeastern United States. We examined the relation of both single SNPs and haplotypes in CD14 with the atopic outcomes.
Two SNPs were significantly associated with eczema. In dominant models adjusted for potential confounders, SNP rs2569193 was associated with significantly decreased risk for eczema (odds ratio [OR] for CT/TT vs CC, 0.5; 95% CI, 0.3-0.8), whereas SNP rs2569190 (also reported as the C-159T) was associated with significantly increased risk for eczema (OR for CT/TT vs CC, 2.3; 95% CI, 1.4-3.8). The CT/TT genotypes of SNP rs2569190 also had higher geometric means of serum IgE than the CC genotype (24.6 vs 15 IU/mL, P = .025). Haplotype analyses provided results similar to those of the single SNP analyses.
Our results contradict previous reports that have found a protective effect of the T allele of SNP rs2569190 (C-159T) against atopic disorders. Nevertheless, these results confirm the importance of polymorphisms in CD14 in the development of atopy, and future studies of this gene region will need to account for linkage disequilibrium and environmental exposures unique to the study population.

0 Followers
 · 
78 Views
  • Source
    • "Wang et al. (21) 2005 Chinese The T allele was associated with elevated IgE when the T allele was part of a haplotype containing a D5S2011 E allele. Litonjua et al. (14) 2005 Caucasian in America Infants with CC/CT genotypes had significantly increase risk for eczema and elevated total IgE. Kedda et al. (41) 2005 Caucasian in Australia There was a weak association (P = 0.084) with the T allele that was associated with atopy. "
    [Show abstract] [Hide abstract]
    ABSTRACT: This review considers the data from studies analysing associations between the CD14C-159T single nucleotide polymorphism (SNP) and asthmatic phenotypes and discusses the variability of the conclusions. By searching PubMed and EMBASE for articles on CD14C-159T -related population or family-based association studies, 47 were identified up till September 2007. Collectively, the studies reviewed herein consistently showed population differences in frequencies of the alleles of the SNP, with African descent having the highest C allele frequencies, followed by Caucasians and Asians. The T allele of the SNP was associated with increased sCD14 in some studies but not in others. Inconsistently, the C allele, or even occasionally the T allele, was associated with atopic phenotypes in a population subgroup. There are several explanations for these inconsistencies, including lack of power, linkage disequilibrium, gene-gene interactions, population admixture and gene-environment interactions. If the SNP was associated with functional changes to the coded protein and thus modulating susceptibility to allergic disease, its effect may be modest and dependent on other co-existent, ethnicity-specific, genetic or environmental risk factors.
    Allergy 12/2008; 63(11):1411-7. DOI:10.1111/j.1398-9995.2008.01804.x · 6.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The biology of the innate immunity receptors is of central importance in the host response to the environment. Identifying genetic variants that alter the innate immune response is highly relevant to understanding asthma pathogenesis. This review summarizes recent studies of the role of innate immunity receptors, including Toll-like receptors and CD14, in the pathogenesis of asthma. The majority of studies published since 2004 have been genetic association studies in various clinical settings, which have found positive associations of single nucleotide polymorphisms in TLR2, TLR4, TLR6 and TLR10 with asthma or atopy, although the number of studies is small and the results not yet replicated. The designs for CD14 genetic studies have been more sophisticated and have included gene-environment interaction. The results of CD14 gene associations with asthma and atopy are suggestive but have not been fully replicated. Potential reasons for non-replication of TLR and CD14 association studies include insufficient power, type I error, population heterogeneity and different phenotypes studied. In addition, there may be differences in CD14 genetic effects between childhood and adulthood, and between levels of endotoxin exposure. The evidence is still being accumulated for the role of Toll-like receptor polymorphisms in the pathogenesis of asthma. There is emerging evidence for the role of CD14 polymorphisms in the development of asthma and atopy. Further studies of innate immunity in asthma and allergy are required, using rigorous study design, measurement of environmental exposure and intermediate phenotypes to demonstrate single nucleotide polymorphism functionality.
    Current Opinion in Allergy and Clinical Immunology 03/2006; 6(1):23-8. DOI:10.1097/01.all.0000200503.77295.bb · 3.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ecotilling is a high-throughput method of discovery and analysis of single-nucleotide polymorphism (SNP) variations in natural populations, but it requires a substantial investment in sophisticated equipment, costly reagents, and specialized software programs and implementation of several time-consuming steps that limit its use in laboratories with modest financial resources. Moreover, labeling efficiency of PCR primers with fluorescent dyes during Ecotilling can be reduced by unwanted exonuclease activity of single strand-specific nucleases. A new alternative protocol involving a simplified gel system, unlabeled primers, DNA staining after single strand-specific nuclease digestion, and standard gel data analysis was optimized to address these constraints. Using this alternative protocol, we successfully identified four new SNPs verified by sequencing in a collection of 57 diverse rice accessions along with 2 previously reported SNPs in a 922-bp DNA region from thealk gene. An SNP cluster containing a deletion within a 472-bp fragment of thewaxy gene was also characterized. In addition, 4 previously reported SNPs in thealk andwaxy genes were faithfully genotyped among the 57 accessions based on comparisons with sequencing results. Associations between the genotyped SNPs and amylose class and starch gelatinization temperature were as anticipated. These results, along with detailed time and cost comparisons between the 2 methods, suggest that alternative Ecotilling is a simple and reproducible method for SNP discovery and genotyping in rice that leads to substantial savings in equipment, reagents, software, and time compared with the standard Ecotilling procedure.
    Plant Molecular Biology Reporter 03/2006; 24(1):3-22. DOI:10.1007/BF02914042 · 2.37 Impact Factor
Show more