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Growing up abolishes a genetic protection against asthma

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Researchers have discovered that the CCR5Δ32 mutation loses its protective effect against asthma as children mature. This may explain conflicting results and means that future association and linkage studies must take account of age as a confounder.

The researchers went back to a population of schoolchildren aged 8–12 years they studied in 1989 and followed up all those available 10 years later—627 of the original 3406 sample—to determine whether as adults their asthma, wheezing, and atopy status had changed according to their mutation status.

Carrying the deletion significantly reduced the risk of having current asthma in childhood (odds ratio (OR) 0.31 (95% confidence interval 0.14 to 0.72)) but not in adulthood (OR 0.88 (95% CI 0.52 to 1.48)), according to logistic regression corrected for atopy (in 1989) and sex. CCR5Δ32 was not associated with current atopy in either study. Wheezing in childhood had the lowest frequency of heterozygous or homozygous carriers whereas wheezing developing in adults or persisting from childhood had a much higher frequency compared with controls without asthma. Overall carrier frequency for CCR5Δ32 was 19%, and the population was in Hardy-Weinberg equilibrium. Mean age was 20 (range 18–22) years, and the two samples were reasonably similar.

The researchers had shown that children aged 5–15 years with CCR5Δ32 mutation were protected from asthma. Contradictory findings from other studies led them to test whether protection might be age dependent. The deletion stops expression of a chemokine receptor on the surface of T helper 1 cells.

Thorax 2003;58:222–226.

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