A Genome-Wide Association Study of Total Serum and Mite-Specific IgEs in Asthma Patients

<div><p>Immunoglobulin E (IgE) is one of the central players in asthma and allergic diseases. Although the serum IgE level, a useful endophenotype, is generally increased in patients with asthma, genetic factors influencing IgE regulation in asthma are still not fully understood. To identify the genetic variations associated with total serum and mite-specific IgEs in asthmatics, a genome-wide association study (GWAS) of 657,366 single nucleotide polymorphisms (SNPs) was performed in 877 Korean asthmatics. This study found that several new genes might be associated with total IgE in asthmatics, such as <i>CRIM1</i> (rs848512, <i>P</i> = 1.18×10⁻⁶; rs711254, <i>P</i> = 6.73×10⁻⁶), <i>ZNF71</i> (rs10404342, <i>P</i> = 7.60×10⁻⁶), <i>TLN1</i> (rs4879926, <i>P</i> = 7.74×10⁻⁶), and <i>SYNPO2</i> (rs1472066, <i>P</i> = 8.36×10⁻⁶; rs1038770, <i>P</i> = 8.66×10⁻⁶). Regarding the association of specific IgE to house dust mites, it was observed that intergenic SNPs nearby to <i>OPRK1</i> and <i>LOC730217</i> might be associated with <i>Dermatophagoides pteronyssinus</i> (D.p.) and <i>Dermatophagoides farinae</i> (D.f.) in asthmatics, respectively. In further pathway analysis, the phosphatidylinositol signaling system and adherens junction pathways were estimated to play a role in the regulation of total IgE levels in asthma. Although functional evaluations and replications of these results in other populations are needed, this GWAS of serum IgE in asthmatics could facilitate improved understanding of the role of the newly identified genetic variants in asthma and its related phenotypes.</p>