Methods: 158 Chinese asthmatic children aged 6-12 years were recruited from our paediatric allergy clinic. These patients were prospectively followed for five years. Pre-bronchodilator spirometry was recorded at baseline and then monitored at least annually. Spirometric indices were compared with local references. Genomic DNA from these patients was genotyped for single-nucleotide polymorphisms (SNPs) on the 10 asthma loci by TaqMan genotyping assays. Generalised estimating equation was used to analyse effects of these SNPs on longitudinal changes in lung function parameters.
Results: The mean (SD) age of patients at baseline was 10.0 (1.8) years, and 104 (66%) of them were male. 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 exposure, ICS treatment and presence of upper respiratory infection within two weeks, rs1342326 of IL33 was significantly 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 SNPs from SLC22A5, IL13, IL2RB, RORA, SMAD3 and IL18R1 did not show significant association with longitudinal 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: Research Grants Council General Research Funds (469908 and 470909); Research Committee Group Research Scheme (3110060) and Direct Grant for Research (2013.2.033) of CUHK