Methods: 158 asthmatic children aged 6-12 years were followed for five years. Pre-bronchodilator spirometry was recorded at least annually. Genomic DNA was genotyped for single-nucleotide polymorphisms (SNPs) on the asthma loci by TaqMan genotyping assays. Generalised estimating equation was used to analyse effects of these SNPs on changes in lung function parameters.
Results: The mean (SD) age of patients at baseline was 10.0 (1.8) years. Twenty-eight percent had passive smoking and 58% ever received inhaled corticosteroid (ICS) treatment during follow-up. About three quarters of these patients had family history of allergies. Rs3894194 and rs9273349 were not genotyped due to unavailable TaqMan assays. Adjusting for age, sex, passive smoking, ICS treatment and preceding upper respiratory infection, rs1342326 of IL33 was associated with FEV1 (B=1.952, P<0.001), FVC (B=1.215, P<0.001), FEV1/FVC (B=0.752, P<0.001) and FEF25-75 (B=1.219, P=0.005). Rs2305480 of GSDMB was also associated with FEV1/FVC (B=0.940, P<0.001). The other six loci did not show significant association with change in any spirometric index.
Conclusions: This is the first Asian study of genetic determinants for lung function growth. IL33 appears to be a candidate gene for longitudinal changes in several spirometric indices among Chinese children with asthma. Larger cohorts are needed to replicate our findings due to low frequency of risk allele in IL33_rs1342326 among our patients.
Funding: Direct Grant for Research (2014.1.063), CUHK