甘露糖结合凝集素基因54号密码子多态性与川崎病易感性的研究

目的　探讨甘露糖结合凝集素 (MBL)基因第 5 4号密码子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 ,对16 0例中国汉族健康儿童及 95例川崎病患儿的MBL基因多态性进行检测。结果　 ( 1)中国汉族健康儿童MBL基因多态性分布与文献报道的香港华人及高加索人种接近 ,无统计学差异。( 2 )川崎病患儿GAC等位基因频率高于健康对照组 ( 0 2 5 8vs 0 138,P <0 0 1) ,而GGC等位基因频率低于健康对照组 ( 0 74 2vs 0 86 2 ,P <0 0 1)。GAC型等位基因与中国汉族儿童川崎病密切相关 [OR =2 18,95 %CI(OR值的 95 %置信区间 )为 1 38～ 3 4 4 ,P <0 0 5 ]。 ( 3)在川崎病患儿中 ,GAC型等位基因携带者其病史有前驱感染史者多于GGC纯合子 (P <0 0 1)。结论　川崎病发病受遗传背景的影响 ,与MBL第 5 4号密码子基因多态性密切相关

Correlation between mannose-binding lectin gene codon 54 polymorphism and susceptibility of Kawasaki disease

OBJECTIVE: Human mannose-binding lectin (MBL) is a C-type serum lectin synthesized by the liver as an acute-phase protein. MBL can bind to glycoproteins terminated with mannose and N-acetylglucosamine present in the cell walls on a variety of microorganisms. Therefore, MBL appears to play an important role in the immune system. Low levels of MBL in human have been associated with a susceptibility to recurrent infections. MBL deficiency and low serum MBL levels are strongly associated with the presence of three point mutations at codon 52, 54 and 57 of exon 1 in the human MBL gene, and in Chinese population, the codon-54 mutation occurs at a frequency of 0.11 - 0.17. The data suggested that MBL insufficiency might also predispose to the development of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). The possibility that Kawasaki disease (KD) is an infectious disease has been discussed and investigated for decades, in light of the implication that infections are involved in the pathogenesis of KD. It has been suggested that MBL insufficiency might predispose to the occurrence of KD. This study was aimed to investigate the genetic association of MBL codon-54 polymorphism in patients with KD, and to investigate possible associations with clinical manifestations of the disease. METHODS: There were 95 patients with KD and 160 healthy subjects in the study. The genotype of MBL gene 54 codon was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Clinical characteristics and biochemical examination were also performed. RESULTS: The genotype frequency of heterozygote (GGC/GAC) was significantly higher in KD group than that in healthy subjects (45.2% vs 25.0%, P < 0.01), and the allele frequency of GAC mutation was also higher in KD patients than that in control group (0.258 vs 0.138, P < 0.01). The variant allele (GAC) was markedly associated with KD (OR = 2.18, 95% CI = 1.38 approximately 3.44, P < 0.05). But there was no significant difference in the allele frequency of GAC between patients with and without coronary artery lesion (CAL) in KD cases (0.281 vs 0.246, P > 0.05). In addition, in cases of KD, more patients carrying the variant allele (GAC) had episodes of upper respiratory or gastrointestinal infections prior to the onset of KD than wild homozygotes (P < 0.01). CONCLUSION: The codon 54 polymorphism of MBL gene was associated with KD. It is possible that MBL gene codon 54 mutation might be related to the pathogenesis of KD.