An Exploratory Pilot Study of Genetic Marker for IgE-Mediated Allergic Diseases with Expressions of Fc epsilon R1 alpha and C epsilon

作者：Liao En Chih; Chang Ching Yun; Hsieh Chia Wei; Yu Sheng Jie; Yin Sui Chu; Tsai Jaw Ji^*

来源：International Journal of Molecular Sciences, 2015, 16(5): 9504-9519.

DOI：10.3390/ijms16059504

• Fc epsilon R1 promoter region
• Fc epsilon R1 mRNA expression
• single nucleotide polymorphism (SNP)
• genetic markers
• allergic diseases

The high affinity immunoglobulin E (IgE) receptor-Fc epsilon R1 is mainly expressed on the surface of effector cells. Cross-linking of IgE Abs bound to Fc epsilon R1 by multi-valent antigens can induce the activation of these cells and the secretion of inflammatory mediators. Since Fc epsilon R1 plays a central role in the induction and maintenance of allergic responses, this study aimed to investigate the association of Fc epsilon R1 with the allergic phenotype of C epsilon expression and cytokine and histamine release from peripheral leukocytes. Peripheral leukocytes from 67 allergic and 50 non-allergic subjects were used for genotyping analysis. Peripheral mononuclear cells (PBMCs) were used for C epsilon expression and ELISpot analysis, while polymorphonuclear cells (PMNs) were used for histamine release. The association between genotype polymorphism of the Fc epsilon R1 promoter region (rs2427827 and rs2251746) and allergic features of C epsilon expression and histamine were analyzed, and their effects on leukocytes function were compared with wild type. The genotype polymorphisms of Fc epsilon R1 promoter region with CT and TT in rs2427827 and TC in rs2251746 were significantly higher in allergic patients than in non-allergic controls. Patients with single nucleotide polymorphism (SNP) of Fc epsilon R1 promoter region had high levels of total IgE, mite-specific Der p 2 (Group 2 allergen of Dermatophagoides pteronyssinus)-specific IgE and IgE secretion B cells. The mRNA expression of Fc epsilon R1 was significantly increased after Der p2 stimulation in PBMCs with SNPs of the Fc epsilon R1 promoter region. Despite the increased C epsilon mRNA expression in PBMCs and histamine release from PMNs and the up-regulated mRNA expression of interleukin (IL)-6 and IL-8 secretions after Der p2 stimulation, there was no statistically significant difference between SNPs of the Fc epsilon R1 promoter region and the wild type. SNPs of Fc epsilon R1 promoter region were associated with IgE expression, IgE producing B cells, and increased Der p2-induced Fc epsilon R1 mRNA expression. These SNPs may be used as a disease marker for IgE-mediated allergic inflammation caused by Dermatophagoides pteronyssinus.

• 出版日期2015-5