Association of IL-10 Promoter Genetic Polymorphisms with the Risk of Kawasaki Disease and Development of Acute Coronary Artery Lesions

• Main Authors: Tsung-jen Lai, 賴琮仁
• Other Authors: Luo-ping Ger
• Format: Others
• Language: en_US
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/5ec5p9

碩士 === 國立中山大學 === 生物醫學研究所 === 97 === Kawasaki disease (KD) is the most common cause of paediatric acquired heart disease which may be attributed to the combined effects of infection, immunological response, and genetic susceptibility. Acute coronary artery lesions (CALs) develop in 20-48 % KD children. In addition, chronic CALs develop in approximately 20-30% of untreated KD children. Although KD children treated with IVIG, 2-6% still develop chronic CALs. According to recent epidemiological studies, Asian populations have a much higher incidence of KD. Taiwan has the third highest annual incidence in the world (69 per 100,000 children < 5 years of age between 2003 and 2006). Several studies have shown that KD patients spontaneously produce high levels of IL- 10. Plasma or serum IL-10 levels of KD children in acute phase were nearly 8-33 fold and 4-5 fold higher than those of healthy controls and those of the acute febrile children, respectively. The elevated IL-10 levels during the acute phase of KD not only decreased during subacute and convalescent phase, but also decreased immediately after IVIG administration, coincidently rapid improvement of inflammatory symptoms. The above studies show a correlation of high IL-10 levels with inflammatory features of KD, but do not answer the question of whether high levels of IL-10 may be simply a byproduct of acute KD, or whether it may play a role in the pathogenesis of KD. Therefore, a family-based linkage study of 134 case-parents trios, a case-control study of 247 KD children and 129 normal controls, and a matched case-control study of 76 KD cases with acute coronary artery lesions (CALs) and 76 KD controls without acute CALs were carried out to evaluate the association of genetic single nucleotide polymorphisms (SNP) in IL-10 promoter (-1082, -819, and -592) with the risk of KD and acute CALs. Based on the Transmission Disequilibrium test (TDT) results, significant undertransmission of haplotype ATA and overtransmission of haplotype (ACC+GCC) were found for KD (p = 0.023 and 0.011, respectively), even after 1,000 times permutation (p = 0.026 and 0.010, respectively). In addition, the TC and CC genotype of IL-10-819T>C were significantly associated with the decreased risk of acute CALs (AOR, 0.93; 95% CI, 0.47-1.81 and AOR, 0.07; 95% CI, 0.01-0.62, respectively), as compared to TT genotype. The carries of AC and CC genotype in IL-10-592A>C were with significantly decreased risk of acute CALs (AOR, 0.90; 95%CI, 0.46-1.75 and AOR, 0.17; 95%CI, 0.03-0.87, respectively), as compared to those with AA genotype. Furthermore, as compared with ATA/ATA diplotype, GCC+ACC/GCC+ACC diplotype of IL10 was associated with the decreased risk of acute CALs (AOR, 0.18; 95% CI, 0.04-0.72). In conclusion, the haplotype and diplotype of IL10-1082/-819/-592 were significant differences in the transmission in KD families and that the IL10-819 and -592 SNPs played important role for the sequelae of acute CALs.