ADAM33 gene polymorphisms associate with asthma susceptibility and severity in East China han population.
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.
Department of Respiratory Medicine, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, PR China.
Zhijun
Z
Jie
Zhilin
Z
Hu
Chunxue
C
Bai
Meiling
M
Jin
D051722:ADAM Proteins / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People; D001249:Asthma / Q000235:genetics* / Q000503:physiopathology; D002681:China; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
D051722:ADAM Proteins; C450441:ADAM33 protein, human