Association between candidate genes and lung function growth in Chinese asthmatic children

Background Asthma is caused by a complex interaction between multiple candidate genes and environmental factors. The Childhood Asthma Management Program reported lung function decline in a significant proportion of Caucasian asthmatic children, but such a relation has not been studied in other populations. Our group recently reported that interleukin-13 (IL13), interleukin-4 receptor-alpha and thymus and the activation-regulated chemokine interacted to influence asthma and raised plasma total IgE. However, there has not been any study that has addressed the genetic influences for longitudinal lung function growth. Objective We studied the longitudinal changes in spirometric variables in Chinese asthmatic children, and investigated the influence and interactions between eight different loci in six candidate genes as well as environmental factors affecting lung function growth in these children. Methods Spirometry was performed at baseline and study completion. Genotyping was performed by restriction fragment length polymorphism. Multi-factor dimensionality reduction (MDR) was used to detect any gene-gene or gene-environment interaction. Results We prospectively followed 131 Chinese children, aged 9.9 (3.0) years, for 4.5 (0.8) years. Their mean (standard deviation) baseline forced expiratory volume in 1 s (FEV1) was 98.6 (20.6)% of predicted, and FEV1 to forced vital capacity (FVC) ratio was 77.8 (11.3)%. FEV1 and FVC increased by 210 (115) and 248 (148) mL/year during this study, and these changes were significantly larger among males (P < 0.0001). Univariate analysis revealed a significant association between annual FEV1 change and C1570T of signal transducer and activator of transcription 6 gene (STAT6; P=0.009). Linear regression confirmed this finding (P=0.041). Using MDR, we detected a significant 3-locus interaction between IL13 R130Q, ADRB2 R16G and STAT6 C1570T for determining change in FVC (P=0.045). Conclusion Our data suggest that STAT6 may influence lung function growth in asthmatic children. We also found significant interactions among several atopy-related genetic polymorphisms for influencing FVC change.