川崎氏症是目前最常見的小兒後天型心臟病，其致病原因可能歸咎於感染、免疫反應及基因易感性的聯合效應，約有20-48%的川崎氏症小孩會併發急性冠狀動脈病變，此外，在沒經過治療的狀況下有將近20-30%的患者會轉變為慢性冠狀動脈病變，即使經過治療，仍有2-6%的患者會轉變為慢性冠狀動脈病變。根據最近的流行病學研究指出，亞洲族群具有較高的發生率，而台灣具有世界第三高的發生率(自2002年至2006年的調查，每十萬名五歲以下的嬰幼兒其年發生率為69名)。許多研究已經指出和正常孩童和急性發燒的病童相比，急性期川崎氏症患者的血漿中的間白質10的量分別高出將近八到三十三倍及四到五倍，在急性期上升的間白質10，不但在亞急性期及恢復期會下降，更在注射靜脈免疫球蛋白後立即下降，迅速的改善免疫病徵，以上的研究顯示了間白質10高表現量和川崎氏症的免疫特徵的相關性，但至今仍無法解釋間白質10是否只是急性期川崎氏症的表現還是其在造成川崎氏症的病理原因上扮演一個重要角色。因此我們以134組父母小孩三人組、247名川崎氏症患者及129名健康控制對照組和76名具有急性冠狀動脈病變的川崎氏症患者及76名不具有急性冠狀動脈病變的川崎氏症患者的配對控制對照組來探討間白質10啟動子(-1082、-819、-592)的基因多型性與川崎氏症及是否併發急性冠狀動脈病變的風險性。根據連鎖不平衡檢定的結果，未傳遞的單基因體型ATA和傳遞的單基因體型(ACC+GCC)具有顯著性差異(p值分別為0.023和0.011)，即使經過1,000次排列計算仍具有顯著性差異(p值分別為0.026和0.010)。此外，和間白質10-819基因型TT相比，基因型TC和CC具有顯著降低急性冠狀動脈病變的風險性(校正勝算比分別為0.93、0.07，95%信賴區間分別為0.47-1.81、0.01-0.62)。和間白質10-592基因型AA相比，基因型AC和CC具有顯著降低急性冠狀動脈病變的風險性(校正勝算比分別為0.90、0.17，95%信賴區間分別為0.46-1.75、0.03-0.87)。更進一步比較，和間白質10雙基因體型ATA/ATA相比，GCC+ACC具有顯著降低急性冠狀動脈病變的風險性(校正勝算比分別為0.18，95%信賴區間分別為0.04-0.72)。因此間白質基因單體型及雙體型在川崎氏症家庭中具有顯著的連鎖傳遞不平衡，而間白質10-819和-592單基因多型性對於是否會併發急性冠狀動脈病變的易感性扮演重要的角色。

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.

1.1 Backgrounds and Significances 12
1.2 Subjects and Methods 21
1.3 Results 25
1.4 Discussion 30
1.5 Tables 36
1.6 References 46

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