ADAM33 polymorphism: association with bronchial hyper-responsiveness in Korean asthmatics

Area of Science:

• Genetics
• Pulmonology
• Biochemistry

Background:

• A disintegrin and metalloprotease 33 (ADAM33) is expressed in lung fibroblasts and bronchial smooth muscle cells.
• ADAM33's structure and location suggest a role in airway remodeling and bronchial hyper-responsiveness.
• Previous studies linked ADAM33 gene polymorphisms to asthma susceptibility in Caucasians.

Purpose of the Study:

• To investigate the association between ADAM33 genetic variants and asthma in a Korean population.
• To examine the relationship between ADAM33 gene polymorphisms, asthma susceptibility, bronchial hyper-reactivity, and serum IgE levels.

Main Methods:

• Genotyping of five specific ADAM33 polymorphisms (S1 G>A, T1 T>C, V-1 C>A, V1 T>A, V4 C>G) in 326 Korean asthmatics and 151 controls.
• Inference of haplotype frequencies using Arlequin software.
• Comparison of allele frequencies and haplotype distributions using logistic regression and general linear models.

Main Results:

• No significant differences in single nucleotide polymorphism (SNP) or haplotype distributions were found between asthmatics and controls.
• The T1 T>C SNP and the ht4 (GCGG) haplotype in ADAM33 showed a significant association with bronchial hyper-reactivity (PC(20) methacholine levels) in asthma patients.
• P-values for the associations were P=0.03 for T1 T>C and P=0.0007 for ht4 using a co-dominant model.

Conclusions:

• ADAM33 gene polymorphism is associated with the development of bronchial hyper-responsiveness in asthma.
• Specific ADAM33 variants may influence airway reactivity in asthmatic individuals.