Associations of genetic variants in ADAM33 and TGF-beta 1 genes with childhood asthma risk

The aim of the present study was to explore the associations of genetic variants in the ADAM33 and TGF-beta 1 genes with the risk of childhood asthma. A total of 299 asthmatic children and 311 healthy controls were recruited in the hospital-based case-control study. The asthmatic subjects were further divided into mild and severe groups according to disease severity. Single-nucleotide polymorphisms (SNP) at ADAM33 V4, T2, S2 and T1, and TGF-beta 1 C-509T and T869C were selected and detected with PCR-RFLP. The associations of the SNPs with asthma risk and severity were analyzed. The associations between the haplotypes of ADAM33 and TGF-beta 1 were also evaluated. Compared with the GG genotype, the GC and CC genotypes at V4 were associated with an increased asthma risk in children and the ORs were 2.92 and 10.56, respectively. Compared with the CC genotype, the CT/TT genotype at C-509T was associated with an increased asthma risk and the OR was 2.26. Subsequent to stratification by asthma severity, compared with the V4 GG genotype, it was found that the CG and CC genotypes were associated with a mild asthma risk and the ORs were 3.00 and 5.99, respectively. The SNP at C-509T (CT/TT vs. CC) was associated with mild asthma (OR= 2.34), whereas a marginally significant association was detected between the SNP (CT/ TT vs. CC) and severe asthma risk (OR= 2.19). The haplotype analysis revealed that, compared with the GGCA haplotype of ADAM33, significant associations of the haplotypes of CGCG, CGGA, GACA, GACG and GAGA with asthma risk were observed, and the ORs were 31.12, 12.24, 4.73, 30.85 and 4.83, respectively. No significant association was detected between the TGF-beta 1 haplotypes and asthma risk. The genetic variants at V4 and C-509T had the potential to modify the childhood asthma risk and the associations showed no notable difference with the disease severity. Thus, ADAM33 haplotypes provided more useful information in the prediction of asthma risk.