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Analysis of Toll-like receptor families participating in the Kawasaki disease and application to a treatment

参与川崎病的Toll样受体家族分析及其在治疗中的应用

基本信息

批准号：
15591116
负责人：
NISHIMURA Shinji
金额：
$ 1.92万
依托单位：
Saga University (2004)佐賀医科大学 (2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

We extracted DNA from whole blood of 69 control children and 67 Kawasaki disease(KD). We determined a polymorphism in the CD14 gene at -159 upstream from the major transcription site (CD14/-159 ) by restriction fragment assay. We then investigated the association between CD14/-159 and onset of KD and development of coronary artery lesion(CAL). 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 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-reacting protein and vascular endothelial growth factor, which had previously been reported as risk factor for CAL, than those with CC genotypes. 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.We were not able to point out the gene seasonal polymorphism about a TLR2 gene and gene seasonal polymorphism of a TLR4 gene. It was thought that this genetic gene seasonal t polymorphism was different with Japanese.The expression of RP105 on B lymphocytes in acute phase of Kawasaki disease let you suggest the possibility that a specific function of RP105 affected the condition of a patient of this disease.

我们从69名正常儿童和67名川崎患儿的全血中提取DNA。我们通过限制性片段分析确定了CD 14基因在主要转录位点上游-159处的多态性（CD 14/-159）。然后我们研究了CD 14/-159与KD发病和冠状动脉病变（CAL）发展之间的关系。该多态性在正常儿童和KD患者中的基因组频率和等位基因频率无差异。CD 14/-159位点TT基因型患儿CAL并发症发生率高于CT和CC（OR，4.05，95%CI，1.34 -12.22）。KD伴CAL组T等位基因频率显著高于C等位基因频率（OR，2.20; 95%CI，1.23 -3.94）。他们的数据在患者中得到证实，无论患者是否接受静脉注射丙种球蛋白治疗。与CC基因型相比，TT基因型KD患者的C反应蛋白和血管内皮生长因子水平显著升高，而这两项先前被报道为CAL的危险因素。这些结果提示，CD 14/-159位点的T等位基因和TT基因型是川崎病CAL的危险因素，并且川崎病CAL的发生可能与CD 14-toll样受体反应的大小有关，我们未能指出TLR 2基因和TLR 4基因的基因季节性多态性。认为该基因的季节性t多态性与日本人不同，川崎急性期B淋巴细胞上RP 105的表达提示RP 105的一种特异性功能可能影响川崎病患者的病情。