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.

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.

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).

We have confirmed an association between polymorphisms in ADAM33 and lung function in early life, suggesting a role for ADAM33 in asthma pathogenesis.