β2-adrenoceptor polymorphisms and asthma from childhood to middle age in the British 1958 birth cohort

a genetic association study

Ian P. Hall, John D. Blakey, Khalid A. Al Balushi, Amanda Wheatley, Ian Sayers, Marcus E. Pembrey, Susan M. Ring, Wendy L. McArdle, David P. Strachan

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

Background: Functionally relevant polymorphisms of the β2-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.

Original languageEnglish
Pages (from-to)771-779
Number of pages9
JournalLancet
Volume368
Issue number9537
DOIs
Publication statusPublished - Aug 26 2006

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Genetic Association Studies
Adrenergic Receptors
Asthma
Respiratory Sounds
Parturition
Gene Frequency
Haplotypes
Genes
Meta-Analysis
Population
Bronchitis
DNA
Respiratory Function Tests
Homozygote
Age of Onset
Interviews
Lung
Incidence

ASJC Scopus subject areas

  • Medicine(all)

Cite this

β2-adrenoceptor polymorphisms and asthma from childhood to middle age in the British 1958 birth cohort : a genetic association study. / Hall, Ian P.; Blakey, John D.; Al Balushi, Khalid A.; Wheatley, Amanda; Sayers, Ian; Pembrey, Marcus E.; Ring, Susan M.; McArdle, Wendy L.; Strachan, David P.

In: Lancet, Vol. 368, No. 9537, 26.08.2006, p. 771-779.

Research output: Contribution to journalArticle

Hall, IP, Blakey, JD, Al Balushi, KA, Wheatley, A, Sayers, I, Pembrey, ME, Ring, SM, McArdle, WL & Strachan, DP 2006, 'β2-adrenoceptor polymorphisms and asthma from childhood to middle age in the British 1958 birth cohort: a genetic association study', Lancet, vol. 368, no. 9537, pp. 771-779. https://doi.org/10.1016/S0140-6736(06)69287-8
Hall, Ian P. ; Blakey, John D. ; Al Balushi, Khalid A. ; Wheatley, Amanda ; Sayers, Ian ; Pembrey, Marcus E. ; Ring, Susan M. ; McArdle, Wendy L. ; Strachan, David P. / β2-adrenoceptor polymorphisms and asthma from childhood to middle age in the British 1958 birth cohort : a genetic association study. In: Lancet. 2006 ; Vol. 368, No. 9537. pp. 771-779.
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T2 - a genetic association study

AU - Hall, Ian P.

AU - Blakey, John D.

AU - Al Balushi, Khalid A.

AU - Wheatley, Amanda

AU - Sayers, Ian

AU - Pembrey, Marcus E.

AU - Ring, Susan M.

AU - McArdle, Wendy L.

AU - Strachan, David P.

PY - 2006/8/26

Y1 - 2006/8/26

N2 - Background: Functionally relevant polymorphisms of the β2-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.

AB - Background: Functionally relevant polymorphisms of the β2-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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