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Genetics of onset of asthma

Dijk, F. Nicole; de Jongste, Johan C.; Postma, Dirkje S.; Koppelman, Gerard H.

Current Opinion in Allergy and Clinical Immunology: April 2013 - Volume 13 - Issue 2 - p 193–202
doi: 10.1097/ACI.0b013e32835eb707
PEDIATRIC ASTHMA AND DEVELOPMENT OF ATOPYREVIEW: Edited by Carlos E. Baena-Cagnani and Leonard B. Bacharier

Purpose of review Most asthma starts early in life. Defining phenotypes of asthma at this age is difficult as many preschool children have asthma-like respiratory symptoms. This review discusses progress in defining early wheezing phenotypes and describes genetic factors associated with the age of onset of asthma.

Recent findings Latent class analyses confirmed transient and persistent wheezing phenotypes, and identified a novel intermediate-onset wheezing phenotype that was strongly associated with atopy and asthma at age 8 years. However, no single cross-sectional or longitudinal definition of respiratory symptoms in childhood strongly predicts asthma later in life. Genome-wide association (GWA) studies have identified a locus on chromosome 17q12–21 (encoding ORMDL3 and GSDMB) as a risk factor for predominantly childhood-onset asthma, but not for atopy, and overall not for adult-onset asthma. Other loci found by GWA studies appear to increase asthma risk both in children and adults. Atopy genes do not explain early-onset asthma.

Summary Although most asthma starts early in life, no valid test is able to identify asthma at that age period. GWA studies have provided more insight into the unique and common genetic origins of adult-onset and childhood-onset asthma. The 17q12–21 locus is predominantly associated with childhood-onset asthma.

aDepartment of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital

bGRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen

cDepartment of Pediatrics, Sophia Children's Hospital, Erasmus University Medical Center, Rotterdam

dDepartment of Pulmonology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

Correspondence to Gerard H. Koppelman, MD, PhD, Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands. Tel: +31 50 3614215; fax: +31 50 3614235; e-mail: g.h.koppelman@umcg.nl

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