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- W1484854539 abstract "Abstract Rationale Specific airway resistance (sR aw ), is a sensitive and reproducible measure of lung function in young children – higher sR aw indicating poorer lung function. We investigated the relationship between single nucleotide polymorphisms (SNPs) in ADAM33 (a disintegrin and metalloprotease 33; Nature 2002;418:426-30) and sR aw at age 5 years in the setting of a prospective birth cohort study. Methods Children (n=504) were gentopyed for 17 SNPs spanning 11Kb of the ADAM33 gene. Lung function at age 5 years was assessed using plethysmographic measurement of sR aw at baseline and after bronchodilator (400 μg albuterol). Results were analyzed using regression analysis. Results Four SNPs showed significant association with sR aw . Children who were homozygous for the rare allele of the F+1 SNP had a significantly higher sR aw than the heterozygotes and wild type homozygotes (kPa/s, GM [95% CI] 1.26 [1.18-1.34] vs 1.15 [1.13-1.17], p=0.0008). Carriers of the rare allele for ST+5 had a lower sR aw than the wild type homozygotes (kPa/s, GM [95% CI] 1.14 [1.12-1.16] vs 1.19 [1.16-1.23], p=0.007). Children who were mutant homozygotes for V-1 (n=5) and T2 (n=4) had significantly higher sR aw values. After administration of the bronchodilator, the association between F+1, V-1 and T2 and sR aw was lost. However, for ST+5, carriers of the rare allele still had significantly lower sR aw (kPa/s GM [95%CI] 0.96 [0.94-0.98] vs 1.01 [0.98-1.04], p=0.005). Conclusions We have confirmed an association between polymorphisms in ADAM33 and lung function in early life, suggesting a role for ADAM33 in asthma pathogenesis." @default.
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- W1484854539 date "2004-02-01" @default.
- W1484854539 modified "2023-10-15" @default.
- W1484854539 title "Manchester asthma and allergy study*1Polymorphisms in ADAM33 predict lung function at age 5 years" @default.
- W1484854539 doi "https://doi.org/10.1016/j.jaci.2004.01.733" @default.
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