title: ADAM33 polymorphism: association with bronchial hyper-responsiveness in Korean asthmatics.
abstract: BACKGROUND
  A disintegrin and metalloprotease 33 (ADAM33) is expressed in the lung by fibroblasts and bronchial smooth muscle cells. Given its structure and cellular provenance, ADAM33 may be associated with airway remodelling and bronchial hyper-responsiveness. Single nucleotide polymorphisms (SNPs) and haplotypes of the ADAM33 gene have previously been associated with asthma susceptibility in the Caucasian population.
  
  
  OBJECTIVE
  To assess whether genetic variants of ADAM33 are related to asthma in a Korean population, we conducted an association study of the ADAM33 gene with asthma susceptibility, bronchial hyper-reactivity and serum IgE in Korean asthmatics (n=326) and normal controls (n=151). Five of the 14 polymorphisms originally reported to be associated with asthma development (S1 G>A, T1 T>C, V-1 C>A, V1 T>A, V4 C>G) were genotyped using single base extension and electrophoresis. Haplotypes and their frequencies were inferred using the algorithm implemented by the software Arlequin. Allele frequencies of each SNP and haplotypes were compared between the patients and the normal controls using logistic regression analysis.
  
  
  RESULTS
  There was no significant difference in the distribution of SNPs and the six haplotypes between asthmatics and normal controls. All single SNPs and six haplotypes in ADAM33 were also analysed for the association with level of PC(20) using general linear models. The distribution of the T1 T>C SNP and one haplotype (ht4: GCGG) showed significant association with log-transformed PC(20) methacholine level in the asthma patients (P=0.03 and 0.0007, respectively, using a co-dominant model).
  
  
  CONCLUSIONS
  Polymorphism of ADAM33 may contribute to development of BHR in asthma.
authors.affiliation: Asthma Genome Research Center, Soonchunhyang University Hospital, Bucheon, Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.forename: H-S
authors.initials: HS
authors.lastname: Park
authors.forename: S W
authors.initials: SW
authors.lastname: Park
authors.forename: A S
authors.initials: AS
authors.lastname: Jang
authors.forename: S T
authors.initials: ST
authors.lastname: Uh
authors.forename: T
authors.initials: T
authors.lastname: Rhim
authors.forename: C-S
authors.initials: CS
authors.lastname: Park
authors.forename: S-J
authors.initials: SJ
authors.lastname: Hong
authors.forename: S T
authors.initials: ST
authors.lastname: Holgate
authors.forename: J W
authors.initials: JW
authors.lastname: Holloway
authors.forename: H D
authors.initials: HD
authors.lastname: Shin
mesh_terms: D051722:ADAM Proteins; D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000235:genetics; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002648:Child; D005260:Female; D006239:Haplotypes; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007723:Korea; D016014:Linear Models; D015810:Linkage Disequilibrium; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D007073:Immunoglobulin E; D051722:ADAM Proteins; C450441:ADAM33 protein, human; D008666:Metalloendopeptidases