de Guia R M, Echavez M D J, Gaw E L C, Gomez M R R, Lopez K A J, Mendoza R C M, Rapsing J M C, Retreta D P, Tubog C M B, Ventolero M H, Yao C L, Ramos J D A
Department of Biochemistry, Faculty of Pharmacy, University of Santo Tomas, Manila, Philippines.
Research Center for the Natural and Applied Sciences, University of Santo Tomas, Manila, Philippines.
Int J Immunogenet. 2015 Jun;42(3):182-9. doi: 10.1111/iji.12200. Epub 2015 Apr 16.
Elevated IgE levels in the atopic triad of asthma, allergic rhinitis and atopic dermatitis is a multifactorial condition whose genetic component involves interaction of several gene loci. One hundred and two matched pairs of allergic and nonallergic individuals were phenotyped for total serum IgE level using enzyme-linked immunosorbent assay (ELISA). Atopic status was defined by serum IgE concentration ≥100 IU mL(-1) . SNPs genotyped include the IL4 -590C>T (rs2243250), FCER1B E237G (rs569108), CD14 -159C>T (rs2569190), IL4RA Q551R (rs1801275) and ADRB2 R16G (rs1042713). Gene-gene interaction was analysed using multifactor-dimensionality reduction (MDR). Significant association between atopic allergy and the IL4 -590C>T polymorphism was confirmed in three genetic models. Interaction among the 5 gene variants was validated by MDR. The five-locus model was chosen as the best to describe the interaction of the SNPs within the context of atopy. The strongest interaction was between IL4 -590C>T and IL4RA Q551R and between FCER1B E237G and ADRB2 R16G. The IL4 variant also interacts synergistically with the FCER1B and ADRB2 coding variants. CD14 -159C>T, in general, interacts antagonistically with the rest of the SNPs. In conclusion, a five-locus interaction exists among IL4 -590C>T, FCER1B E237G, CD14 -159C>T, IL4RA Q551R and ADRB2 R16G in Filipino cases of atopic allergy.
在哮喘、过敏性鼻炎和特应性皮炎这一特应性三联征中，免疫球蛋白E（IgE）水平升高是一种多因素疾病，其遗传成分涉及多个基因座的相互作用。使用酶联免疫吸附测定（ELISA）对102对匹配的过敏个体和非过敏个体进行总血清IgE水平的表型分析。特应性状态由血清IgE浓度≥100 IU/mL定义。基因分型的单核苷酸多态性（SNP）包括白细胞介素4（IL4）-590C>T（rs2243250）、高亲和力IgE受体β链（FCER1B）E237G（rs569108）、脂多糖结合蛋白（CD14）-159C>T（rs2569190）、白细胞介素4受体α链（IL4RA）Q551R（rs1801275）和β2肾上腺素能受体（ADRB2）R16G（rs1042713）。使用多因素降维法（MDR）分析基因-基因相互作用。在三种遗传模型中证实了特应性过敏与IL4 -590C>T多态性之间存在显著关联。通过MDR验证了5个基因变异之间的相互作用。选择五位点模型作为描述特应性背景下SNP相互作用的最佳模型。最强的相互作用存在于IL4 -590C>T与IL4RA Q551R之间以及FCER1B E237G与ADRB2 R16G之间。IL4变异体还与FCER1B和ADRB2编码变异体协同相互作用。总体而言，CD14 -159C>T与其他SNP相互拮抗。总之，在菲律宾特应性过敏病例中，IL4 -590C>T、FCER1B E237G、CD14 -159C>T、IL4RA Q551R和ADRB2 R16G之间存在五位点相互作用。
