Effect of 17q21 Variants and Smoking Exposure in Early-Onset Asthma

• Published in: The New England journal of medicine Vol. 359; no. 19; pp. 1985 - 1994
• Main Authors: Bouzigon, Emmanuelle, Corda, Eve, Aschard, Hugues, Dizier, Marie-Hélène, Boland, Anne, Bousquet, Jean, Chateigner, Nicolas, Gormand, Frédéric, Just, Jocelyne, Le Moual, Nicole, Scheinmann, Pierre, Siroux, Valérie, Vervloet, Daniel, Zelenika, Diana, Pin, Isabelle, Kauffmann, Francine, Lathrop, Mark, Demenais, Florence
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 06.11.2008
• Subjects: Adolescent; Adult; Age; Age of Onset; Aged; Asthma; Asthma - genetics; Biological and medical sciences; Child; Chromosomes, Human, Pair 17 - genetics; Environmental Exposure - adverse effects; Families & family life; Female; General aspects; Genetic Markers; Genetic Predisposition to Disease; Genetics; Genome-Wide Association Study; Genotype; Humans; Life Sciences; Male; Medical sciences; Middle Aged; Phenotype; Polymorphism, Single Nucleotide; Regression Analysis; Risk Factors; Santé publique et épidémiologie; Tobacco smoke; Tobacco Smoke Pollution - adverse effects; Tobacco, tobacco smoking; Toxicology; Lung disease; Genetic variability; Respiratory disease; Tobacco smoking; Genotype; Exposure; Asthma; Medicine; Variant; Tobacco; Age of onset; Chromosome E17; Bronchus disease; Early; Obstructive pulmonary disease
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa0806604

A locus on chromosome 17 has previously been shown to be associated with susceptibility to asthma. This study shows that the association is specific to early-onset asthma (occurring at the age of 4 years or younger) in those exposed to environmental tobacco smoke in early life. The study implicates markers regulating at least two genes — ORMDL3 and GSDML — in determining susceptibility. This study shows that the association between a locus on chromosome 17 and asthma is specific to early-onset asthma in those exposed to environmental tobacco smoke in early life. The study implicates markers regulating at least two genes — ORMDL3 and GSDML — in determining susceptibility. A consensus is emerging that asthma is not a single disease but rather a collection of separate entities with variable expression over the life span. Although various asthma phenotypes have been identified with the use of clinical criteria, 1 little is known about their cause. The identification of their determinants is an important step toward understanding the physiopathology of asthma. One of the simplest criteria that can be used to differentiate asthma phenotypes is the age at onset. Longitudinal studies have shown that phenotypic features correlate with the age at the onset of asthma in children and adults 2 – 5 and that . . .