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Polymorphisms in a disintegrin and metalloprotease 33 (ADAM33)predict impaired early-life lung function.

Simpson, A, Maniatis, N, Jury, F, Cakebread, J, Lowe, L, Holgate, S, Woodcock, AA, Ollier, WER, Collins, A, Custovic, A, Holloway, J, John, S

Am J Respir Crit Care Med. 2005;172(1):55-60.

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Abstract

Rationale: Asthma commonly originates in early life in association with impaired lung function that tracks to adulthood.Objectives: Within the context of a prospective birth cohort study weinvestigated the association between single nucleotide polymorphisms(SNPs) in a disintegrin and metalloprotease 33 (ADAM33) gene andearly-life lung function. Methods: Children were genotyped for 17 SNPs inADAM33. Lung function at age three (n=285) and five years (n=470) wasassessed using plethysmographic measurement of specific airway resistance(sRaw). At age five we also measured FEV1. SNPs were analyzed individuallyusing logistic regression, followed by linkage disequilibrium (LD) mappingto identify the causal locus. Main Results: Carriers of the rare allele ofF+1 SNP had reduced lung function at age three years (p=0.003). When therecessive model was considered, four SNPs (F+1, S1, ST+5, V4) showedassociation with sRaw at age five years (p<0.04). Using LD mapping, wefound evidence of a significant causal location between BC+1 and F1 SNPs,at the 5' end of the gene. Four SNPs were associated with lower FEV1 (F+1,M+1, T1 and T2, p</=0.04). The risk of transient early wheezing morethan doubled amongst children homozygous for the A allele of F+1 (oddsratio 2.39, 95% confidence intervals 1.18-4.86, p=0.02), but there was noassociation between any SNP and allergic sensitization orphysician-diagnosed asthma. Conclusions: Polymorphisms in ADAM33 predictimpaired early life lung function. The functionally relevant polymorphismis likely to be at the 5' end of the gene.

Bibliographic metadata

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Published date:
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Volume:
172(1)
Start page:
55
End page:
60
Pagination:
55-60
Digital Object Identifier:
10.1164/rccm.200412-1708OC
Access state:
Active

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:1d10460
Created:
29th August, 2009, 15:37:15
Last modified:
29th September, 2015, 13:31:41

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