title: 17q21 variants modify the association between early respiratory infections and asthma.
abstract: Single nucleotide polymorphisms (SNPs) at chromosome 17q21 confer an increased risk of early-onset asthma. The objective was to study whether 17q21 SNPs modify associations between early respiratory infections and asthma. Association analysis was conducted in 499 children (268 with asthma, median age 11 yrs) from the Epidemiological Study on the Genetics and Environment of Asthma (EGEA). The 12-yr follow-up data were used to assess persistent or remittent asthma in young adulthood. Respiratory infection before 2 yrs of age was assessed retrospectively. For the 12 17q21 SNPs studied, the odds ratios (OR) for association between infection and early-onset asthma (age at onset <or=4 yrs) were higher in carriers of risk genotypes (OR 3.42-6.36) than in noncarriers (OR 1.84-2.44; p-value for interaction 0.02-0.04 for five SNPs). Risk genotypes also increased the association between infection and childhood asthma that remits in adulthood (OR 4.84-7.16 in carriers and 1.74-2.25 in noncarriers; p-value for interaction 0.008-0.05 for 10 SNPs). In children with 17q21 risk genotypes and early-life environmental tobacco smoke (ETS) exposure, associations between infection and asthma were further enhanced. 17q21 genetic variants and early ETS exposure enhance the association between early respiratory infections and early-onset asthma and childhood asthma that remits in adulthood.
authors.affiliation: Institute for Risk Assessment Sciences, Division of Environmental Epidemiology, Utrecht Univeristy, P.O. Box 80178, Utrecht, The Netherlands. L.A.Smit@uu.nl
authors.forename: L A M
authors.initials: LA
authors.lastname: Smit
authors.forename: E
authors.initials: E
authors.lastname: Bouzigon
authors.forename: I
authors.initials: I
authors.lastname: Pin
authors.forename: V
authors.initials: V
authors.lastname: Siroux
authors.forename: F
authors.initials: F
authors.lastname: Monier
authors.forename: H
authors.initials: H
authors.lastname: Aschard
authors.forename: J
authors.initials: J
authors.lastname: Bousquet
authors.forename: F
authors.initials: F
authors.lastname: Gormand
authors.forename: J
authors.initials: J
authors.lastname: Just
authors.forename: N
authors.initials: N
authors.lastname: Le Moual
authors.forename: R
authors.initials: R
authors.lastname: Nadif
authors.forename: P
authors.initials: P
authors.lastname: Scheinmann
authors.forename: D
authors.initials: D
authors.lastname: Vervloet
authors.forename: M
authors.initials: M
authors.lastname: Lathrop
authors.forename: F
authors.initials: F
authors.lastname: Demenais
authors.forename: F
authors.initials: F
authors.lastname: Kauffmann
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001249:Asthma / Q000209:etiology* / Q000235:genetics*; D002648:Child; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012141:Respiratory Tract Infections / Q000150:complications* / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D014028:Tobacco Smoke Pollution / Q000009:adverse effects; D000094524:Gasdermins
chemical_list: D008565:Membrane Proteins; D009363:Neoplasm Proteins; D014028:Tobacco Smoke Pollution; C527978:GSDMB protein, human; D000094524:Gasdermins; C464399:ORMDL3 protein, human