Allergy Asthma Immunol Res.  2015 May;7(3):249-255. 10.4168/aair.2015.7.3.249.

Association of Single Nucleotide Polymorphisms in the MD-2 Gene Promoter Region With Der p 2 Allergy

• Liao EC
• Chang CY
• Wu CC
• Wang GJ
• Tsai JJ

• KMID: 2260462
• DOI: http://doi.org/10.4168/aair.2015.7.3.249

Abstract

PURPOSE
Sensitization to house dust mite (Dermatophagoides pteronyssinus) is a considerable risk factor for the progression of allergic disease. The group 2 allergen from Dermatophagoides pteronyssinus, Der p 2, is considered a major one in patients with specific immunoglobulin E (IgE) to Der p 2. Der p 2 has structural homology with myeloid differentiation 2 (MD-2), which is involved in the lipopolysaccharide-binding component of the Toll-like receptor 4 signaling pathway and the development of inflammation. The aim of this study was to examine the genetic association of single nucleotide polymorphisms (SNPs) in the promoter region of MD-2 with Der p 2-sensitive allergy.
METHODS
We investigated associations between cohort's characteristics, including 280 allergic and 80 healthy subjects by examining total IgE, eosinophils, D. pteronyssinus-specific IgE, Der p 2-specific IgE, the number of IgE-producing B cells induced by Der p 2, and the odds ratio of allergic symptoms.
RESULTS
Based on the 1,000 genome project data, the minor allele frequencies of the rs1809441 and rs1809442 are 0.467 and 0.474, respectively. However, the correlation of linkage disequilibrium (LD) between these 2 SNPs is D'=1, the genotype frequencies of the 2 MD-2 (LY96) SNPs (rs1809441 and rs1809442) that are located nearby were significantly different between allergic and health subjects: the TT genotype of rs1809441 and the GG genotype of rs1809442 were more frequent in allergic subjects than in healthy subjects (16.1% vs 2.5% in both genotypes). The allergic patients with these genotypes exhibited significantly higher levels of D. pteronyssinus-specific IgE and Der p 2-specific Ig E, and a larger number of Der p 2-activated B cells. In addition, these 2 SNPs in the MD-2 promoter region were significantly associated with the prevalence of nasal, skin, and asthmatic allergic symptoms.
CONCLUSIONS
Our results indicated that 2 SNPs in the MD-2 promoter region were significantly associated with Der p 2-specific Ig E, and thereby suggest that these SNPs may play a major role in susceptibility to Der p 2-triggered immune responses in a Taiwanese population.

Keyword

Dermatophagoides pteronyssinus; myeloid differentiation-2 (MD-2); Der p 2; single nucleotide polymorphisms (SNPs); mite allergy

MeSH Terms

B-Lymphocytes
Dermatophagoides pteronyssinus
Eosinophils
Gene Frequency
Genome
Genotype
Humans
Hypersensitivity*
Immunoglobulin E
Immunoglobulins
Inflammation
Linkage Disequilibrium
Odds Ratio
Polymorphism, Single Nucleotide*
Prevalence
Promoter Regions, Genetic*
Pyroglyphidae
Risk Factors
Skin
Toll-Like Receptor 4
Immunoglobulin E
Immunoglobulins
Toll-Like Receptor 4

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