rs2251746

A retrospective cohort study of 282 patients with severe uncontrolled asthma treated with omalizumab, mepolizumab, or benralizumab for 12 months evaluated genetic variants in 11 genes (IL1RL1, IL5, GATA2, IKZF2, RAD50, C3, FCER1A, FCER1B, FCGR2A, FCGR2B, FCGR3A) as predictors of response. Key findings: FCGR2B rs3219018-C, GATA2 rs4857855-T, and FCGR2A rs1801274-AG associated with improved lung function in omalizumab (p=0.052, 0.052, 0.012); IL1RL1 rs17026974-AG/GG associated with reduced exacerbations in omalizumab (p=0.040, 0.041); FCER1B rs569108-AA and FCGR2A rs1801274-GG associated with corticosteroid reduction in benralizumab; FCER1A rs2427837-A associated with improved lung function in mepolizumab (p=0.023).

Case-control genome-wide association study of 1,878 glioma cases and 3,670 controls examining associations between asthma/allergy susceptibility variants and glioma risk. SNP rs7216389 at 17q21 (ORMDL3) was significantly associated with increased glioma risk (OR=1.10, 95% CI: 1.01-1.19, P=0.022), providing genetic evidence for a positive association between asthma susceptibility and glioma risk, contrary to epidemiological studies reporting inverse associations.

This functional study demonstrates that the FcεRIα gene -18483A>C polymorphism (rs2494262) affects transcriptional activity through preferential YY1 transcription factor binding to the -18483C allele, resulting in lower transcriptional activity compared to the -18483A allele. The effect was confirmed via electrophoretic mobility shift assay, chromatin immunoprecipitation, luciferase reporter assays across multiple cell lines, and YY1 knockdown experiments.