IL4Rα and ADAM33 as genetic markers in asthma exacerbations and type-2 inflammatory endotype.
Clin Exp Allergy
; 47(8): 998-1006, 2017 Aug.
Article
en En
| MEDLINE
| ID: mdl-28326636
ABSTRACT
BACKGROUND:
Genetic markers of susceptibility to asthma exacerbations in adults remain unclear.OBJECTIVE:
To identify genetic markers of asthma exacerbations, particularly in patients with type-2 inflammatory endotype.METHODS:
In this observational study of patients enrolled in the Kinki Hokuriku Airway disease Conference multicenter study, frequency of exacerbations requiring systemic corticosteroids during 2 years after enrolment and associated risk factors was determined. For genetic marker analysis, interleukin-4 receptor α (IL4RA) rs8832 and a disintegrin and metalloprotease 33 (ADAM33) S_2 (rs528557), T_1 (rs2280091), T_2 (rs2280090), and V_4 (rs2787094) variants were included. Elevated serum periostin levels at enrolment (≥95 ng/mL, defined as type-2 inflammatory endotype) were considered in the analysis.RESULTS:
Among 217 patients who were successfully followed up for 2 years after enrolment, 60 patients showed at least one asthma exacerbation during the 2 years. Airflow limitation (%FEV1 <80%) and recent exacerbations but not genetic variants were identified as risk markers of exacerbations. A total of 27 patients showed type-2 inflammatory endotype (serum periostin ≥95 ng/mL at enrolment) and subsequent exacerbations; risk factors in these patients were airflow limitation (odds ratio, 6.51; 95% confidence interval (CI) 2.37-18.6; P=.0003), GG genotype of IL4RA rs8832 (odds ratio, 4.01; 95% CI 1.47-11.0; P=.007), and A allele of ADAM33 T_2 (odds ratio, 2.81; 95% CI 1.05-7.67; P=.04) by multivariate analysis. In addition, GG genotype of IL4RA rs8832 was associated with type-2 endotype, whereas A allele of ADAM33 T_2 was associated with mixed type of eosinophilic/type-2 and neutrophilic inflammations. CONCLUSIONS AND CLINICAL RELEVANCE IL4RA and ADAM33 variants may be risk markers of asthma exacerbations in type-2 inflammatory endotype. Precise endotyping may facilitate the identification of genetic risk markers of asthma exacerbations.Palabras clave
Texto completo:
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Banco de datos:
MEDLINE
Asunto principal:
Asma
/
Proteínas ADAM
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Subunidad alfa del Receptor de Interleucina-4
Tipo de estudio:
Clinical_trials
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Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Aged
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Humans
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Middle aged
Idioma:
En
Año:
2017
Tipo del documento:
Article