Research article summary (published 24 Aug 2006):

Beta2-adrenoceptor polymorphisms and asthma from childhood to middle age in the British 1958 birth cohort: a genetic association study.

Full Abstract

BACKGROUND:
Functionally relevant polymorphisms of the beta2-adrenoceptor gene (ADRB2) are common in white populations, but their contribution to the burden of airways disease in the population is uncertain. We aimed to relate the long-term prevalence of asthma or wheeze to functional coding region polymorphisms in the ADRB2 gene.

METHODS:
The British 1958 birth cohort consisted of all people born in Britain during a week in 1958. Asthma, wheezy bronchitis, and wheezing were ascertained by interview at ages 7, 11, 16, 23, 33, and 42 years, and lung function tests at 35 and 45 years. DNA samples from 8018 participants in the 45-year follow-up were genotyped for three coding variants in the ADRB2 gene. We extend the follow-up of this nationwide cohort by a further 10 years and relate asthma prevalence, prognosis, and lung function to functional coding region polymorphisms in the ADRB2 gene in the cohort members who contributed DNA samples. We also compared and combined our findings with those reaching significance in two previous meta-analyses.

FINDINGS:
Half the cohort (4105 of 8018) had some history of wheezing illness by age 42 years. Neither lifetime prevalence nor age at onset were related to ADRB2 coding variants. However, the common polymorphisms Arg16Gly (rs1042713, Arg 16 allele frequency 36.3%) and Gln27Glu (rs1042714, Glu 27 allele frequency 44.6%) were significantly associated with persistence of asthmatic symptoms from childhood to middle age. Among homozygotes for the Arg16-Gln27 haplotype at these loci, 19.3% (41 of 212) childhood wheezers had five or more wheezing episodes in the past year at age 42, compared with 11.9% (71 of 599) with no copy of this haplotype. However, only 3% of all frequent adult wheezing was statistically attributable to this haplotype. The less common Thr164Ile polymorphism (rs1800888, Ile allele frequency 1.5%) was not a major predictor of either frequency or prognosis of asthma. Our data do not support the findings of previous meta-analyses when considered in isolation or when combined with their contributory studies.

INTERPRETATION:
ADRB2 polymorphisms might predict a small component of the long-term prognosis in childhood asthma, but are not important determinants of asthma incidence or prevalence in the British population.

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Author information

Author/s: Hall, Ian P (IP); Blakey, John D (JD); Al Balushi, Khalid A (KA); Wheatley, Amanda (A); Sayers, Ian (I); Pembrey, Marcus E (ME); Ring, Susan M (SM); McArdle, Wendy L (WL); Strachan, David P (DP);

Affiliation: Division of Therapeutics and Molecular Medicine, University of Nottingham, UK. Ian.Hall(-atsign-)nottingham.ac.uk

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Lancet (Lancet), published in England. (Language: eng)

Reference: 2006-Aug; vol 368 (issue 9537) : pp 771-9

Dates: Created 2006/08/28; Completed 2006/09/07; Revised 2006/11/15;

PMID: 16935688, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

Comments and Corrections

CommentIn: Lancet. 2006 Aug 26;368(9537):710-1. (PMID: 16935668)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adult Asthma - epidemiology; genetics Child Genotype Great Britain - epidemiology

Humans Polymorphism, Genetic Prevalence Receptors, Adrenergic, beta-2 - genetics Respiratory Sounds

Associated Chemicals: Receptors, Adrenergic, beta-2 (0)

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