Department of Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany.
Pediatr Allergy Immunol. 2013 Aug;24(5):441-9. doi: 10.1111/pai.12083. Epub 2013 Jun 3.
Recently, three genome-wide association studies (GWAS) demonstrated FCER1A, the gene encoding a ligand-binding subunit of the high-affinity IgE receptor, to be a major susceptibility locus for serum IgE levels. The top association signal differed between the two studies from the general population and the one based on an asthma case-control design. In this study, we investigated whether different FCER1A polymorphisms are associated with total serum IgE in the general population and asthmatics specifically.
Nineteen polymorphisms were studied in FCER1A based on a detailed literature search and a tagging approach. Polymorphisms were genotyped by the Illumina HumanHap300Chip (6 polymorphisms) or MALDI-TOF MS (13 polymorphisms) in at least 1303 children (651 asthmatics) derived from the German International Study of Asthma and Allergies in Childhood II and Multicentre Asthma Genetics in Childhood Study.
Similar to two population-based GWAS, the peak association with total serum IgE was observed for SNPs rs2511211, rs2427837, and rs2251746 (mean r(2) > 0.8), with the lowest p-value of 4.37 × 10(-6). The same 3 polymorphisms showed the strongest association in non-asthmatics (lowest p = 0.0003). While these polymorphisms were also associated with total serum IgE in asthmatics (lowest p = 0.003), additional polymorphisms (rs3845625, rs7522607, and rs2427829) demonstrated associations with total serum IgE in asthmatics only (lowest p = 0.01).
These data suggest that FCER1A polymorphisms not only drive IgE levels in the general population but that specific polymorphisms may also influence IgE in association with asthma, suggesting that disease-specific mechanisms in IgE regulation exist.
最近，三项全基因组关联研究（GWAS）表明，编码高亲和力 IgE 受体配体结合亚基的 FCER1A 基因是血清 IgE 水平的主要易感基因座。两项基于普通人群和哮喘病例对照设计的研究之间的顶级关联信号不同。在这项研究中，我们调查了不同的 FCER1A 多态性是否与普通人群和哮喘患者的总血清 IgE 相关。
根据详细的文献检索和标记方法，在 FCER1A 中研究了 19 个多态性。多态性通过 Illumina HumanHap300Chip（6 个多态性）或 MALDI-TOF MS（13 个多态性）在至少 1303 名儿童（651 名哮喘患者）中进行基因分型，这些儿童来自德国儿童期哮喘和过敏国际研究 II 和多中心儿童期哮喘遗传学研究。
与两项基于人群的 GWAS 相似，与总血清 IgE 最强关联的是 SNPs rs2511211、rs2427837 和 rs2251746（平均 r(2) > 0.8），最低 p 值为 4.37×10(-6)。在非哮喘患者中，同样的 3 个多态性显示出最强的关联（最低 p = 0.0003）。虽然这些多态性也与哮喘患者的总血清 IgE 相关（最低 p = 0.003），但其他多态性（rs3845625、rs7522607 和 rs2427829）仅在哮喘患者中与总血清 IgE 相关（最低 p = 0.01）。
这些数据表明，FCER1A 多态性不仅驱动普通人群的 IgE 水平，而且特定的多态性也可能影响与哮喘相关的 IgE，表明 IgE 调节存在疾病特异性机制。
