1Equally contributed as first authors.
ADAM33 polymorphism: association with bronchial hyper-responsiveness in Korean asthmatics
Article first published online: 14 JUN 2004
Clinical & Experimental Allergy
Volume 34, Issue 6, pages 860–865, June 2004
How to Cite
Lee, J. H., Park, H.-S., Park, S. W., Jang, A. S., Uh, S. T., Rhim, T., Park, C.-S., Hong, S.-J., Holgate, S. T., Holloway, J. W. and Shin, H. D. (2004), ADAM33 polymorphism: association with bronchial hyper-responsiveness in Korean asthmatics. Clinical & Experimental Allergy, 34: 860–865. doi: 10.1111/j.1365-2222.2004.01977.x
- Issue published online: 14 JUN 2004
- Article first published online: 14 JUN 2004
- Submitted 19 September 2003; revised 4 February 2004; accepted 24 March 2004
- ADAM33 gene;
- bronchial hyper-reactivity;
- Korean population
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 and Methods 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 PC20 using general linear models. The distribution of the T1 T>C SNP and one haplotype (ht4: GCGG) showed significant association with log-transformed PC20 methacholine level in the asthma patients (P=0.03 and 0.0007, respectively, using a co-dominant model).
Conclusion Polymorphism of ADAM33 may contribute to development of BHR in asthma.