A functional polymorphism (-603A --> G) in the tissue factor gene promoter is associated with adult-onset asthma.
Tissue factor (TF) is important for initiation of coagulation and for the increased thrombin activity observed at sites of inflammation. Thrombin activity is induced by allergen challenge in asthmatic airways and is involved in the pathogenesis of asthma. A -603A --> G polymorphism (rs1361600) in the promoter region of the TF gene has been associated with serum TF levels and with the development of cardiovascular diseases. The aim of this study was to determine whether the functional -603A --> G polymorphism has genetic influences on the development of asthma. Case-control analysis was performed of the association between six common single-nucleotide polymorphisms (SNPs), including the -603A --> G polymorphism, at the TF gene, and the development of asthma, using two unrelated Japanese populations. In the primary population (n=826), the GG genotype at the -603A --> G polymorphism was associated with adult-onset asthma (onset at >or=21 years of age) (odds ratio (OR) 2.886, P=0.0231). A second population showed a similar tendency (n=1654, OR 1.602, P=0.064). Transcriptional activity of promoters with -603A --> G genotypes were examined using luciferase promoter assays. The -603G allele was associated with higher promoter activity (P<0.05). The association between the functional polymorphism (-603A --> G) in the TF gene promoter and adult-onset asthma indicates that TF is a candidate gene contributing to asthma susceptibility.
First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Akira
A
Isada
Satoshi
S
Konno
Nobuyuki
N
Hizawa
Mayumi
M
Tamari
Tomomitsu
T
Hirota
Michishige
M
Harada
Yukiko
Y
Maeda
Takeshi
T
Hattori
Ayumu
A
Takahashi
Masaharu
M
Nishimura
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D001249:Asthma / Q000453:epidemiology* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007564:Japan / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D015203:Reproducibility of Results; D013925:Thromboplastin / Q000235:genetics*; D014158:Transcription, Genetic; D055815:Young Adult
D009687:Nuclear Proteins; D013925:Thromboplastin