ADAM33 Gene Polymorphisms Associate with Asthma Susceptibility and Severity in East China Han Population

Abstract

Objective. Multiple genetic and environmental factors impact the pathogenesis of asthma. ADAM33 (a disintegrin and metalloproteinase domain 33) represents a novel susceptibility gene for asthma in several diverse populations. The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) of the ADAM33 gene associate with asthma susceptibility and severity in the Chinese Han population. Methods. A total of 224 subjects were enrolled, including 74 normal controls and 150 asthmatic patients. The asthmatic enrollees were further categorized into high- or low-severity groups according to the percentage of forced expiratory volume in 1 second of predicted value, symptoms, nighttime awakening, requirement for short-acting β2-agonist, and interference with normal activities. Six SNPs (F + 1, ST + 4, S1, S2, T1, and T2) in ADAM33 were genotyped using the polymerase chain restriction fragment length polymorphism method. Results. Three SNPs (F + 1, T1, and T2) of ADAM33 were found to have significant associations with asthma in the study population (p = .0058−.0067). The allele frequencies of two SNPs (F + 1, T1) in both the low- and high-severity groups were significantly different from the allele frequency in the control group. The allelic frequency of the T2 SNP was significantly different from that of the control group only in the high-severity group (p = .0081). Haplotype analysis demonstrated that the frequency of 7575G, 12433T, and 12462C (GTC haplotype) is higher in healthy controls than amongst asthma patients (78.4% vs. 61.8%, p = .0004). Conclusions. Polymorphisms of the ADAM33 gene associate with asthma susceptibility in the east China Han population, and the genetic association is stronger in high-severity asthmatics.

• ADAM33
• asthma
• single nucleotide polymorphism
• susceptibility gene

Acknowledgments

We express our gratitude to the Zhongshan Hospitals for the collection of patients with asthma and healthy controls. We thank the staff at the State Key Laboratory of Genetic Engineering (SKLGE) in Fudan University to help us complete genotyping. We also thank the patients and healthy controls who agreed to participate in this study. This study was supported by grants from the Scientific Development Foundation of the Board of Health in Shanghai (No. 034094) and by the Shanghai Leading Academic Discipline Project, NO B115.

Declaration of Interest

The authors report no conflicts of interests. The authors alone are responsible for the content and writing of this article. And this article received no funding from outside agencies, organizations, or companies. We confirm that the manuscript has been submitted solely to this journal and is not published, in press, or submitted elsewhere and that all the research meets the ethical guidelines, including adherence to the legal requirements of the study country.