肿瘤坏死因子α和白细胞介素10基因启动子区多态性与川崎病的相关性研究  

The correlation between Kawasaki disease and polymorphisms of tumor necrosis factor alpha and interleukin-10 gene promoter

作　　者：杨军[1] 李成荣[1] 李永柏[1] 李若馨[1] 孙来保[1] 黄惠君[1] 王国兵[1] 

机构地区：[1]深圳市儿童医院儿科研究所,518026

出　　处：《中华儿科杂志》2003年第8期598-602,共5页Chinese Journal of Pediatrics

摘　　要：目的　探讨肿瘤坏死因子α(TNF 浕)和白细胞介素 10 (IL 10 )基因启动子区多态性与中国汉族儿童川崎病的易感性和临床表型的关系。方法　应用聚合酶链反应 限制性内切酶片段长度多态性分析 (PCR RFLP)方法检测TNF 浕和ＩＬ 10基因启动子区 4个多态性位点 ,对 96例川崎病患儿及 16 0例正常对照儿童进行相关性分析。结果　 (1)中国汉族健康儿童TNF 浕基因 30 8(A/G)位点等位基因频率与日本人和美国白人正常人群相近 ;而IL 10基因 10 82 (G/A)、 819(C/T)、 5 92 (A/C) 3个位点等位基因频率与英国正常人群差异有显著性 (P均 <0 .0 1) ;(2 )TNF 浕基因 30 8位点等位基因频率在川崎病组和健康对照组间差异无显著性 ;IL 10 10 82、 819、 5 92的 3个位点等位基因频率和单体型在两组之间比较差异亦无显著性 ;(3)临床表型分析发现 ,TNF α 30 8A基因型在静脉注射免疫球蛋白 (IVIG)非敏感型川崎病患者中的发生频率高于TNF α 30 8G基因型 ,比较差异有显著性 (6 7%vs5 % ,χc2 =90 4 8,P <0 0 1) ,前者发生静脉注射用IVIG非敏感型川崎病的相对危险度 (RR)是后者的4 2 2 5倍 (RR 95 %CI=15 81～ 112 88,P <0 0 1)。IL 10 10 82A/ 819T/ 5 92A单体型在川崎病合并冠状动脉损伤患者中的发生频率高于NonObjective Kawasaki disease (KD) is an acute febrile vasculitic syndrome of unknown etiology that preferentially affects coronary artery. It has been suggested that proinflammatory cytokines like tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) are key players during acute KD. Recently, the polymorphisms relative to major transcriptional start site of TNF-α and IL-10 gene were shown to influence the level of TNF-α and IL-10 production in vitro . This study was aimed to investigate the genetic association of TNF-α and IL-10 promoter polymorphisms in juvenile patients of Han nationality with KD, and to investigate the possible associations with clinical manifestations of the disease. Methods Four polymorphism sites of TNF-α and IL-10 gene promoter regions from 96 children with KD were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). One handred and sixty age-matched normal children of the Han nationality were used as control. All patients accepted Doppler echocardiography examination in order to differentiate coronary artery lesions. Results There was significant difference in allele frequencies of -308(A/G) site of the TNF-α gene between children of the Han nationality and those of Japanese and Caucasian in America. There were significant differences in the allele frequencies of -1082(G/A), -819(C/T) and -592(A/C) of IL-10 gene between children of the Han nationality and their British Counterparts ( P <0.01). There was no significant difference in allele frequencies of -308(A/G) site of TNF-α gene between children with KD and normal controls. There was no significant difference in the haplotypes and the allele frequencies of the above three sites of IL-10 between the two groups. However, when clinical features were examined, the genotype frequency of TNF-α-308A was significantly higher in IVIG-resistant KD patients than that of TNF-α-308G genotype (67% vs 5%, χ_c 2=90.48, P <0.01). The genotype of TNF-α-308A was closely associated with

关 键 词：肿瘤坏死因子Α 白细胞介素10 基因启动子 基因多态性 川崎病 粘膜皮肤淋巴结综合征 

分 类 号：R725.4[医药卫生—儿科]