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Updated: Sep 14, 2025

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Independent association of a 17q21 variant with exacerbations in type 2-low adult asthma
Yumi Ishiyama1, Hisako Matsumoto1,2, Hironobu Sunadome1
1Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Background:
The genetic factors contributing to exacerbations in type 2-low asthma are not well understood.
Objective:
We sought to clarify the association between variants in gasdermin B/orosomucoid-like 3 (GSDMB/ORMDL3) on 17q21 and exacerbations in type 2-low asthma.
Methods:
This follow-up study of the multicenter Kinki Hokuriku Airway disease Conference (KiHAC) enrolled adults with asthma who were receiving inhaled corticosteroids. It examined associations between asthma exacerbations requiring systemic corticosteroids over 2 years and clinical and genetic factors in patients with the type 2-low endo-genotype, defined by serum periostin levels lower than 95 ng/mL and the IL4RA rs8832 A allele. Exacerbation risks were also evaluated in patients with the type 2-low genotype, defined by both the POSTN rs3829365 C allele and the IL4RA rs8832 A allele, using the KiHAC and replication cohorts. The genetic variant rs7216389 in GSDMB was the primary focus for assessing genetic risk.
Results:
A total of 115 patients with the type 2-low endo-genotype were analyzed (mean age, 62 years; 76.5% female). During the 2-year follow-up, 32 patients experienced 1 or more exacerbation. Multivariate analysis identified the rs7216389 TT genotype, recent exacerbations, female sex, and higher body mass index as independent risk factors for asthma exacerbations in patients with the type 2-low endo-genotype. The association between the rs7216389 TT genotype and exacerbations was confirmed in patients with the type 2-low genotype in the KiHAC (n = 89) and replication (n = 125) cohorts.
Conclusions:
The rs7216389 TT variant on 17q21 may be an independent risk factor for exacerbations in adults with type 2-low asthma, highlighting the role of GSDMB in its pathophysiology.
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