Association of CCR5Delta32 with reduced risk of childhood but not adult asthma

P. Srivastava, Peter Joseph Benedict Helms, Diane Linda Stewart, Margaret Jessie Campbell Main, George Russell

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Background: A number of potential candidate genes have been implicated in the pathogenesis of asthma. A 32 base pair deletion in the CCR5 gene renders this chemokine receptor non-functioning and has been shown to be associated with a reduced prevalence of asthma in childhood. The mechanism may be related to impairment of pathogen entry into cells and modified host inflammatory response. We sought to determine the influence of the CCR5A32 mutation on asthma and allergy in the transition from childhood to adulthood.

Methods: 627 individuals first studied as part of a whole population schoolchildren cohort in 1989 when aged 8-12 years were followed up 10 years later for respiratory and allergy symptoms and laboratory markers of atopy. CCR5A32 status was also characterised and the association with childhood and adulthood symptoms determined.

Results: The follow up sample was representative of the original cohort except for a slightly greater prevalence of symptomatic individuals. As children, none who were homozygous for the CCR5A32 mutation had a current physician's diagnosis of asthma. In multivariate analysis and controlling for known confounders, the protective effect of carrying the allele in childhood was highly significant (OR 0.31, 95% Cl 0. 14 to 0.72, p=0.006). There was no protective association with "current asthma" as classified in adulthood within the some population. Subjective or laboratory markers of atopy in childhood or adulthood were not associated with the CCR5A32 mutation. Methacholine bronchial hyperresponsiveness in adulthood was also unrelated to gene carrier status.

Conclusions: In a population with a high allelic frequency for the CCR5A32 mutation, a significant protection against childhood asthma is evident which is independent of atopy. This protection is lost in p the transition between childhood and early adulthood. The contribution of different genetic candidates to the expression of asthma may change with advancing maturity and confound the interpretation of association and linkage studies unless age is taken into account.

Original languageEnglish
Pages (from-to)222-226
Number of pages4
JournalThorax
Volume58
Issue number3
DOIs
Publication statusPublished - 2003

Keywords

  • CCR5 GENE
  • INFLAMMATORY RESPONSE
  • SCHOOLCHILDREN
  • PREVALENCE
  • RESISTANCE
  • SYMPTOMS
  • CHILDREN
  • DELETION
  • DISEASES
  • ALLELE

Cite this

Srivastava, P., Helms, P. J. B., Stewart, D. L., Main, M. J. C., & Russell, G. (2003). Association of CCR5Delta32 with reduced risk of childhood but not adult asthma. Thorax, 58(3), 222-226. https://doi.org/10.1136/thorax.58.3.222

Association of CCR5Delta32 with reduced risk of childhood but not adult asthma. / Srivastava, P.; Helms, Peter Joseph Benedict; Stewart, Diane Linda; Main, Margaret Jessie Campbell; Russell, George.

In: Thorax, Vol. 58, No. 3, 2003, p. 222-226.

Research output: Contribution to journalArticle

Srivastava, P, Helms, PJB, Stewart, DL, Main, MJC & Russell, G 2003, 'Association of CCR5Delta32 with reduced risk of childhood but not adult asthma', Thorax, vol. 58, no. 3, pp. 222-226. https://doi.org/10.1136/thorax.58.3.222
Srivastava P, Helms PJB, Stewart DL, Main MJC, Russell G. Association of CCR5Delta32 with reduced risk of childhood but not adult asthma. Thorax. 2003;58(3):222-226. https://doi.org/10.1136/thorax.58.3.222
Srivastava, P. ; Helms, Peter Joseph Benedict ; Stewart, Diane Linda ; Main, Margaret Jessie Campbell ; Russell, George. / Association of CCR5Delta32 with reduced risk of childhood but not adult asthma. In: Thorax. 2003 ; Vol. 58, No. 3. pp. 222-226.
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abstract = "Background: A number of potential candidate genes have been implicated in the pathogenesis of asthma. A 32 base pair deletion in the CCR5 gene renders this chemokine receptor non-functioning and has been shown to be associated with a reduced prevalence of asthma in childhood. The mechanism may be related to impairment of pathogen entry into cells and modified host inflammatory response. We sought to determine the influence of the CCR5A32 mutation on asthma and allergy in the transition from childhood to adulthood.Methods: 627 individuals first studied as part of a whole population schoolchildren cohort in 1989 when aged 8-12 years were followed up 10 years later for respiratory and allergy symptoms and laboratory markers of atopy. CCR5A32 status was also characterised and the association with childhood and adulthood symptoms determined.Results: The follow up sample was representative of the original cohort except for a slightly greater prevalence of symptomatic individuals. As children, none who were homozygous for the CCR5A32 mutation had a current physician's diagnosis of asthma. In multivariate analysis and controlling for known confounders, the protective effect of carrying the allele in childhood was highly significant (OR 0.31, 95{\%} Cl 0. 14 to 0.72, p=0.006). There was no protective association with {"}current asthma{"} as classified in adulthood within the some population. Subjective or laboratory markers of atopy in childhood or adulthood were not associated with the CCR5A32 mutation. Methacholine bronchial hyperresponsiveness in adulthood was also unrelated to gene carrier status.Conclusions: In a population with a high allelic frequency for the CCR5A32 mutation, a significant protection against childhood asthma is evident which is independent of atopy. This protection is lost in p the transition between childhood and early adulthood. The contribution of different genetic candidates to the expression of asthma may change with advancing maturity and confound the interpretation of association and linkage studies unless age is taken into account.",
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TY - JOUR

T1 - Association of CCR5Delta32 with reduced risk of childhood but not adult asthma

AU - Srivastava, P.

AU - Helms, Peter Joseph Benedict

AU - Stewart, Diane Linda

AU - Main, Margaret Jessie Campbell

AU - Russell, George

PY - 2003

Y1 - 2003

N2 - Background: A number of potential candidate genes have been implicated in the pathogenesis of asthma. A 32 base pair deletion in the CCR5 gene renders this chemokine receptor non-functioning and has been shown to be associated with a reduced prevalence of asthma in childhood. The mechanism may be related to impairment of pathogen entry into cells and modified host inflammatory response. We sought to determine the influence of the CCR5A32 mutation on asthma and allergy in the transition from childhood to adulthood.Methods: 627 individuals first studied as part of a whole population schoolchildren cohort in 1989 when aged 8-12 years were followed up 10 years later for respiratory and allergy symptoms and laboratory markers of atopy. CCR5A32 status was also characterised and the association with childhood and adulthood symptoms determined.Results: The follow up sample was representative of the original cohort except for a slightly greater prevalence of symptomatic individuals. As children, none who were homozygous for the CCR5A32 mutation had a current physician's diagnosis of asthma. In multivariate analysis and controlling for known confounders, the protective effect of carrying the allele in childhood was highly significant (OR 0.31, 95% Cl 0. 14 to 0.72, p=0.006). There was no protective association with "current asthma" as classified in adulthood within the some population. Subjective or laboratory markers of atopy in childhood or adulthood were not associated with the CCR5A32 mutation. Methacholine bronchial hyperresponsiveness in adulthood was also unrelated to gene carrier status.Conclusions: In a population with a high allelic frequency for the CCR5A32 mutation, a significant protection against childhood asthma is evident which is independent of atopy. This protection is lost in p the transition between childhood and early adulthood. The contribution of different genetic candidates to the expression of asthma may change with advancing maturity and confound the interpretation of association and linkage studies unless age is taken into account.

AB - Background: A number of potential candidate genes have been implicated in the pathogenesis of asthma. A 32 base pair deletion in the CCR5 gene renders this chemokine receptor non-functioning and has been shown to be associated with a reduced prevalence of asthma in childhood. The mechanism may be related to impairment of pathogen entry into cells and modified host inflammatory response. We sought to determine the influence of the CCR5A32 mutation on asthma and allergy in the transition from childhood to adulthood.Methods: 627 individuals first studied as part of a whole population schoolchildren cohort in 1989 when aged 8-12 years were followed up 10 years later for respiratory and allergy symptoms and laboratory markers of atopy. CCR5A32 status was also characterised and the association with childhood and adulthood symptoms determined.Results: The follow up sample was representative of the original cohort except for a slightly greater prevalence of symptomatic individuals. As children, none who were homozygous for the CCR5A32 mutation had a current physician's diagnosis of asthma. In multivariate analysis and controlling for known confounders, the protective effect of carrying the allele in childhood was highly significant (OR 0.31, 95% Cl 0. 14 to 0.72, p=0.006). There was no protective association with "current asthma" as classified in adulthood within the some population. Subjective or laboratory markers of atopy in childhood or adulthood were not associated with the CCR5A32 mutation. Methacholine bronchial hyperresponsiveness in adulthood was also unrelated to gene carrier status.Conclusions: In a population with a high allelic frequency for the CCR5A32 mutation, a significant protection against childhood asthma is evident which is independent of atopy. This protection is lost in p the transition between childhood and early adulthood. The contribution of different genetic candidates to the expression of asthma may change with advancing maturity and confound the interpretation of association and linkage studies unless age is taken into account.

KW - CCR5 GENE

KW - INFLAMMATORY RESPONSE

KW - SCHOOLCHILDREN

KW - PREVALENCE

KW - RESISTANCE

KW - SYMPTOMS

KW - CHILDREN

KW - DELETION

KW - DISEASES

KW - ALLELE

U2 - 10.1136/thorax.58.3.222

DO - 10.1136/thorax.58.3.222

M3 - Article

VL - 58

SP - 222

EP - 226

JO - Thorax

JF - Thorax

SN - 0040-6376

IS - 3

ER -