Association between PRKG1 gene and gene-environment interactions with pediatric asthma.

OBJECTIVE: To investigate the relationship between single nucleotide polymorphisms (SNPs) of cGMP-dependent protein kinase I (PRKG1) gene and gene-environment interactions with bronchial asthma in children. METHODS: 109 asthma patients and 158 healthy controls from the General Hospital of Northern Theater Command were enrolled, based case-control study. The iMLDR® multiple SNP typing technique was applied to detect the genotypes of rs7903366, rs7081864, rs7070958 and rs7897633 in PRKG1 gene. The percentage of eosinophils (EOS%) in peripheral blood and serum immunoglobulin E (IgE) in the case group were also measured. Gene-environment interactions were examined using the generalized multi-factor dimensionality reduction (GMDR) method. RESULTS: There were polymorphisms in four SNPs of PRKG1 gene in the case and control groups. The genotype and allele frequencies distribution of rs7897633 demonstrated statistical significance (p < 0.05). There were no statistically significant differences in EOS% and IgE among genotypes at the four SNPs of PRKG1 gene (p > 0.05). The haplotypes CAGA and TGAC presented significant association with asthma risk (p < 0.05). The four-factor model indicated a potential gene-environment interaction in rs7897633, allergen exposure, residence, and environmental tobacco smoke (ETS) exposure (p < 0.05). CONCLUSIONS: The rs7897633 in PRKG1 gene was associated with susceptibility to childhood asthma, and C allele is a protective factor. The haplotype CAGA had a protective effect against asthma risk and TGAC was linked to the high risk of developing asthma. Moreover, the interaction of rs7897633, allergen exposure, residence, and ETS exposure conferred susceptibility to childhood asthma.

Association of GAB1 gene with asthma susceptibility and the efficacy of inhaled corticosteroids in children.

Asthma is a polygenic disease that may onset during childhood. Inhaled corticosteroids (ICS) are the main therapy in asthma, although their efficacy varies among individuals. Nuclear factor κB (NF-κB) is an important target of ICS treatment of asthma. Recent research has reported that GRB2 associated binding protein 1 (GAB1) gene may participate in the pathogenesis of asthma by regulating the NF-κB pathway. Therefore, we used the technique of an improved multiplex ligation detection reaction to sequence GAB1 gene and investigated the involvement of Single-nucleotide variants (SNVs) in GAB1 gene in asthma and ICS efficacy in asthmatic children. We found no differences between asthma cases and controls in allele or genotype frequencies of GAB1. Haplotype analysis showed an increased tendency for AGGAGC frequency in asthma patients compared with controls (OR = 2.69, p = 0.018). The percentage of EOS and genotype distribution of rs1397527 were associated (p = 0.007). The EOS percentage was higher in GT genotype when compared to the GG genotype (5.50 vs 3.00, Bonferroni adjusted p = 0.005). After 12-weeks ICS treatment, GAB1 rs1397527 TT and GT genotype carriers had a smaller change in forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) than GG carriers (p = 0.009), and rs3805236 GG and AG genotype carriers also had a smaller change in FEV1/FVC than AA carriers (p = 0.025). For ICS response, the frequency of GG genotype of rs1397527 was significantly higher in good responders (p = 0.038). The generalized multifactor dimensionality reduction (GMDR) analysis showed a best significant four-order model (rs1397527, allergen exposure, environmental tobacco smoke exposure, and pet exposure) involving gene-environment interactions (p = 0.001). In summary, we found that GAB1 SNVs were not associated with asthma susceptibility. Haplotype AGGAGC was a risk factor for asthma. GAB1 variants were associated with eosinophils and ICS response in asthmatics. Furthermore, gene-environment interaction was observed.