A polymorphism in the promoter of the CD14 gene (CD14/-159) is associated with the development of coronary artery lesions in patients with Kawasaki disease

A polymorphism in the promoter of the CD14 gene (CD14/-159) is associated with the development of coronary artery lesions in patients with Kawasaki disease
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DOI:
10.1067/s0022-3476(03)00330-5
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发表时间:
2003-09-01
影响因子:
5.1
通讯作者:
Hamasaki, Y
Hamasaki, Y
中科院分区:
医学2区
文献类型:
--
作者:
Nishimura, S;Zaitsu, M;Hamasaki, Y

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目的探讨CD 14基因多态性与川崎病(Kawasaki disease,KD)发病的关系。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(CD 14/-159)上游-159位点的多态性。结果CD 14/-159基因多态性在正常儿童和KD患者中的基因频率和等位基因频率无显著性差异。CD 14/-159位点TT基因型的川崎病患儿CAL并发症发生率高于CT和CC基因型患儿(OR为4.05; 95% CI为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。结论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,KD患儿CAL的发生可能与CD 14 Toll样受体反应的强度有关。
Objective To investigate whether a polymorphism in the CD14 gene is associated with Kawasaki disease (KD).Study design We extracted DNA from the whole blood of 69 control children and 67 patients with KD. We determined a polymorphism in the CD14 gene at position -159 upstream from the major transcription site (CD14/-159) by restriction fragment assay. We then investigated the association between CD14/-159 and the onset of KD and development of coronary artery lesion (CAL).Results 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 the 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-reactive protein and vascular endothelial growth factor, which had previously been reported as risk factors for CAL, than those with CC genotypes.Conclusion 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 maybe related to the magnitude of CD14 toll-like receptor response.