A polymorphism in the promoter of the CD14 gene (CD14/-159) is associated with the development of coronary artery lesions in patients with Kawasaki disease.
OBJECTIVE
To investigate whether a polymorphism in the CD14 gene is associated with Kawasaki disease (KD).


METHODS
We extracted DNA from the whole blood of 69 control children and 67 patients with KD. We determined a polymorphism in the CD14 gene at position -159 upstream from the major transcription site (CD14/-159) by restriction fragment assay. We then investigated the association between CD14/-159 and the onset of KD and development of coronary artery lesion (CAL).


RESULTS
The genomic and allelic frequencies of the polymorphism were not different between normal children and KD patients. The KD patients with TT genotypes at CD14/-159 had more CAL complications than those with CT and CC (OR, 4.05; 95% CI, 1.34-12.22). The frequencies of the T allele was significantly higher than that of the C allele in KD patients with CAL (OR, 2.20; 95% CI, 1.23-3.94). Their data were confirmed in the patients whether the patients were treated with intravenous gamma-globulin. KD patients with TT genotypes had significantly higher levels of C-reactive protein and vascular endothelial growth factor, which had previously been reported as risk factors for CAL, than those with CC genotypes.


CONCLUSIONS
These results indicate that the T allele and TT genotype at CD14/-159 are risk factors for CAL in KD, and that the development of CAL in KD may be related to the magnitude of CD14 toll-like receptor response.
D000970:Antineoplastic Agents / Q000097:blood; D002675:Child, Preschool; D003324:Coronary Artery Disease / Q000097:blood / Q000209:etiology* / Q000235:genetics*; D016228:Endothelial Growth Factors / Q000097:blood; D005260:Female; D005838:Genotype; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000235:genetics*; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000097:blood / Q000150:complications* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D000970:Antineoplastic Agents; D016228:Endothelial Growth Factors; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor