Asthma has a strong genetic component. The final disease phenotype results from complex interactions between environment and multiple genes of small-to-modest effects. We investigated whether the polymorphism in genes encoding inflammatory mediators and
cytokines is important for solving the onset and progression of
asthma. We investigated whether 31 single nucleotide polymorphisms (SNPs) in genes encoding
cytokines or
monokines (
interleukin [IL]-5R,
matrix metalloproteinase [
MMP] 8, beta2
adrenergic receptor,
cytotoxic T-lymphocyte-associated antigen 4, IL-3,
C-reactive protein,
cytochrome P450 (CYP) 2C9,
CYP3A4, a
disintegrin and
metalloproteinase [ADAM] 33,
cysteinyl leukotriene receptor [CysLTR] 1, CysLTR2, eosinophilic cationic
protein,
glucocorticoid receptor, and
leukotriene A 4 hydrolase) are related to
asthma development in 206 Japanese
bronchial asthma patients and 127 healthy controls. Using multifactor dimensionality reduction (MDR), we identified rs17099451 in MMP8, using a single locus model, with a mean cross-validation of 87.0%. Using a two-locus model, combinations of MMP8 and rs44707 in ADAM33, and MMP8 and rs40401 in
IL-3, were identified, with mean cross-validation consistencies reaching 45.0%. Of the SNPs selected by the MDR method, rs17099451 in MMP8 and rs40401 in
IL-3 were regarded as the most significant results in a 2 × 2 dominant model analysis. The finding that an MMP8 allele was most strongly related to
asthma development indicates that
metalloproteinase function is crucial to the airflow limitation process involved in this disease.