Association of Single Nucleotide Polymorphisms in the MD-2 Gene Promoter Region With Der p 2 Allergy.
OBJECTIVE
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.
Center for Translational Medicine, Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.; Department of BioIndustry Technology, Da Yeh University, Changhua, Taiwan.; Department of Medical Technology, Jen-Ten College of Medicine, Nursing and Management, Miaoli, Taiwan.
En Chih
EC
Liao
Division of Allergy, Immunology & Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
Ching Yun
CY
Chang
Department of Mechanical Engineering, National Chung-Hsing University, Taichung, Taiwan.
Chia Che
CC
Wu
Graduate Institute of Biomedical Engineering, National Chung-Hsing University, Taichung, Taiwan.
Gou Jen
GJ
Wang
Division of Allergy, Immunology & Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.; College of Life Sciences, National Chung-Hsing University, Taichung, Taiwan.; Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan. jawji@vghtc.gov.tw.
Jaw Ji
JJ
Tsai
Der p 2; Dermatophagoides pteronyssinus; mite allergy; myeloid differentiation-2 (MD-2); single nucleotide polymorphisms (SNPs)