Abstract
Genetic polymorphisms influence the magnitude of the cytokine response after an inflammatory stimulus. To determine whether such polymorphisms might play a role in Kawasaki disease (KD), we analyzed white and Japanese children with KD and control populations for two polymorphic loci in which the A allele is associated with high tumor necrosis factor-α secretion. The lymphotoxin-α+250 A/A genotype was overrepresented among white children with KD compared with controls (0.59 versus 0.36;p = 0.013). The tumor necrosis factor-α−308 A/G genotype was overrepresented among whites with KD who had coronary artery abnormalities compared with those with normal echocardiograms (0.36 versus 0.09;p = 0.044). No significant difference was seen at either locus between Japanese children with KD and Japanese controls. The increased frequency of the high secretor alleles in white children with KD suggests that these loci may be related to susceptibility to KD and to outcome after disease.
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Abbreviations
- KD:
-
Kawasaki disease
- CAA:
-
coronary artery aneurysms
- TNF-α:
-
tumor necrosis factor-α
- LT-α:
-
lymphotoxin-α
- sIL-2R:
-
soluble IL-2 receptor
- IFN-γ:
-
interferon-γ
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Acknowledgements
The authors thank Shelley Bakalis, Chisato Shimizu, and Sachiko Suematsu for collecting and extracting the DNA samples and Shoichi Oyama, Saiseiki Kawaguchi Hospital, for contributing samples.
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Supported in part by the Crippled Children’s Foundation (M.W.Q.), the American Heart Association Southeast Affiliate (M.W.Q., Q.Z.), the Kawasaki Disease Research Program at the UCSD School of Medicine, the Pediatric Pharmacology Research Unit (NIH #2U01HD31318), and an NIH training grant (#MO1RR00827 to D.E.B.).
This work was presented in part at the Infectious Disease Society of America, Denver, CO, U.S.A., November 1998; the Sixth International Kawasaki Disease Symposium, Waikaloa, HI, U.S.A., February 1999; and the Society for Pediatric Research, San Francisco, CA, U.S.A., May 1999.
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Quasney, M., Bronstein, D., Cantor, R. et al. Increased Frequency of Alleles Associated with Elevated Tumor Necrosis Factor-α Levels in Children with Kawasaki Disease. Pediatr Res 49, 686–690 (2001). https://doi.org/10.1203/00006450-200105000-00013
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DOI: https://doi.org/10.1203/00006450-200105000-00013
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