Independent association of a 17q21 variant with exacerbations in type 2-low adult asthma.

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 () 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 rs8832 A allele. Exacerbation risks were also evaluated in patients with the type 2-low genotype, defined by both the rs3829365 C allele and the rs8832 A allele, using the KiHAC and replication cohorts. The genetic variant rs7216389 in 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 in its pathophysiology.