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Association of Genetic Polymorphisms of Cytokines with Kawasaki Disease

Kawasaki disease (KD) is an acute febrile vasculitic syndrome of unknown etiology that preferentially affects the coronary artery. Several lines of evidence point to an important role of genetic variation in KD susceptibility. Acute KD is associated with systemic immune activation, including elevated serum levels of IL-1, IL-4, IL-6, IL-8, IL-10, TNF£\, and decreased serum levels of TGF£], as well as a variety of other cytokines that are believed to play important roles in the onset of KD. This study aims to investigate the association of 14 various polymorphisms of nine cytokine genes (IL-1A, IL-1B, IL-1RN, IL-4, IL-6, IL-8, IL-10, TNFA and TGFB) with the risk of KD. A total of 213 KD children and 226 sex-matched infection disease-free adult controls were recruited in the hospital-based case-control study. The polymorphisms of IL-1 RN intron2 VNTR and IL-4 intron3 VNTR were determined by PCR. The polymorphisms of IL-1B T-31C and IL-1B C-511T were determined by PCR-RFLP. The other single nucleotide polymorphisms (SNPs) of IL-1A C-889T, IL-4 T-590C, IL-6 G-174C, IL-8 T-251A, IL-8 C+781T, IL-10 A-1082G, IL-10 T-819C, IL-10 A-592C, TNFA G-308A and TGFB C-509T were determined by TaqMan real-time PCR method. We found that there were no associations between the 14 polymorphisms and risk of KD, either in the single locus genetypic analysis or in the multiple loci haplotypic analysis. However, in the combined analysis, subjects with four and five ¡§at risk¡¨ genotypes combined from IL-1A, IL-1B, IL-1RN, IL-4, IL-6, IL-8, IL-10, TNFA and TGFB genetic polymorphisms were with 1.85 fold risk of KD as compared to those with less or equl to four ¡§at risk¡¨ genotypes (AOR=1.85; 95% CI, 1.16-2.97; P=0.011). Additionally, subjects with six and seven ¡§at risk¡¨ genetic polymorphisms were with 2.34 fold risk as compared to those with less or equal to four ¡§at risk¡¨ genotypes (AOR=2.34; 95% CI, 1.45-3.76; P=0.001). In conclusion, no association was found between cytokine genetic polymorphisms and KD risk, except in the combined analysis.

Identiferoai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0727109-233049
Date27 July 2009
CreatorsChiao, Ya-hui
ContributorsCheng, Jiin-Tsuey, Ken-Pen Weng, Luo-Ping Ger, Kai-Sheng Hsieh
PublisherNSYSU
Source SetsNSYSU Electronic Thesis and Dissertation Archive
LanguageCholon
Detected LanguageEnglish
Typetext
Formatapplication/pdf
Sourcehttp://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0727109-233049
Rightsnot_available, Copyright information available at source archive

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