title: Association of haplotypes of beta2-adrenoceptor polymorphisms with lung function and airway responsiveness in a pediatric cohort.
abstract: We evaluated the influence of haplotypes of beta(2)-adrenergic receptor (ADRB2) polymorphisms on lung function and airway responsiveness (AR) in a pediatric cohort recruited before birth and followed up to 11 years of age. The subjects (180) were the participants in a prospective study of lung function and AR. They have been assessed five times (at 1 month, 6 months, 12 months, 6 and 11 years of age) for lung function and AR. The two ADRB2 single nucleotide polymorphisms (SNPs): Arg16Gly and Gln27Glu were genotyped by PCR-RLFP and their haplotypes inferred using the program PHASE. An association between the haplotype arg16gln27 and the prevalence of positive AR was found at age 6 years (P = 0.009). The gly16gln27 haplotype was associated with higher FEV1 (P = 0.015) at age 6 and both higher FEV1 and FVC (P = 0.018 and P = 0.001, respectively) at age 11. In contrast, arg16gln27 was associated with both lower FEV1 and FVC (P = 0.028 and P = 0.011, respectively) at age 11. Children with the gly16gln27 haplotype were less likely to have asthma-ever or doctor-diagnosed asthma at age 11 (OR: 0.38; P = 0.019 and OR: 0.31; P = 0.041, respectively). In conclusion, haplotypes of beta(2)-adrenoceptor polymorphisms are associated with lung function, AR, and asthma susceptibility in childhood.
authors.affiliation: School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia, Australia. Bradz@ichr.uwa.edu.au
authors.forename: G
authors.initials: G
authors.lastname: Zhang
authors.forename: C M
authors.initials: CM
authors.lastname: Hayden
authors.forename: S-K
authors.initials: SK
authors.lastname: Khoo
authors.forename: I A
authors.initials: IA
authors.lastname: Laing
authors.forename: S
authors.initials: S
authors.lastname: Turner
authors.forename: L
authors.initials: L
authors.lastname: Landau
authors.forename: J
authors.initials: J
authors.lastname: Goldblatt
authors.forename: P N
authors.initials: PN
authors.lastname: Le Souëf
mesh_terms: D000403:Airway Resistance / Q000502:physiology*; D001249:Asthma / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors
chemical_list: D018343:Receptors, Adrenergic, beta-2