The ADAM33 S2 Polymorphism Is Associated with Susceptibility to Pediatric Asthma in the Chinese Han Population

Abstract

Background: The disintegrin and metalloprotease domain containing protein 33 (ADAM33) is a novel susceptibility gene for asthma and airway hyperresponsiveness, particularly in the Asian population. We investigated the influence of ADAM33 polymorphisms on the serum levels of ADAM33 and the susceptibility to pediatric asthma in the Chinese Han population. Methods: Polymerase chain reaction-restriction fragment length polymorphism analysis was employed to study the genotypic distribution of F+1, T1, and S2 in ADAM33 in a cohort of 120 pediatric asthma patients and 105 healthy controls. The serum levels of secreted ADAM33 protein were measured in all the study subjects using the enzyme-linked immunosorbent assay (ELISA). Results: This case-control study showed that the distribution of F+1 and T1 genotypes of ADAM33 was not significantly different between pediatric asthma patients and healthy controls (p > 0.05); however, the genotype and allele frequencies of the S2 polymorphism were significantly different between asthmatic patients and healthy controls (both p < 0.05). In addition, the frequency of CGC and CGG haplotypes exhibited statistically significant differences, with lower CGC and higher CGG frequencies found in the case group compared to the control group. Finally, in comparison to healthy controls, the serum levels of ADAM33 protein were significantly lower in patients carrying the S2 polymorphism. Conclusion: Our results provide evidence that the ADAM33 S2 polymorphism is associated with increased susceptibility to pediatric asthma and that the CGG haplotype for the F+1, T1, and S2 polymorphisms is associated with an elevated risk of pediatric asthma in the Han population, whereas the CGC haplotype appears to confer a protective effect. Our results may prove useful for population-based screening to affect early intervention.