Genetic variations in the receptor-ligand pair CCR5 and CCL3L1 are important determinants of susceptibility to Kawasaki disease
Genetic variations in the receptor-ligand pair CCR5 and CCL3L1 are important determinants of susceptibility to Kawasaki disease
复制标题
DOI：
10.1086/430953
复制
发表时间：
2005-07-15
影响因子：
6.4
通讯作者：
Ahuja, SK
中科院分区：
文献类型：
--
作者：
Burns, JC;Shimizu, C;Ahuja, SK
川崎是一种发生于儿童期的神秘的自限性血管炎，并发冠状动脉瘤。与欧洲人群相比，亚洲人群中KD的高发病率促使人们寻找在这些人群中差异分布并影响KD易感性的遗传多态性。在这里，我们证明了CCR 5-Delta 32等位基因的全球分布与KD发病率之间的显著负相关。在164个KD患者-父母三人组中，包括CCR 5-Delta 32等位基因在内的4种CCR 5单倍型从杂合子父母差异传递给受影响的儿童。然而，与CCR 5-Delta 32等位基因和某些CCR 5单倍型相关的KD风险降低的幅度在还具有高拷贝数的编码CCL 3L 1（最有效的CCR 5配体）的基因的个体中显著更大。这些研究结果来自任何系统性血管炎的最大遗传研究，表明CCR 5-CCL 3L 1基因-基因相互作用在KD易感性中的核心作用以及基因修饰剂在感染性疾病中的重要性。
Kawasaki disease (KD) is an enigmatic, self-limited vasculitis of childhood that is complicated by development of coronary-artery aneurysms. The high incidence of KD in Asian versus European populations prompted a search for genetic polymorphisms that are differentially distributed among these populations and that influence KD susceptibility. Here, we demonstrate a striking, inverse relationship between the worldwide distribution of CCR5-Delta 32 allele and the incidence of KD. In 164 KD patient-parent trios, 4 CCR5 haplotypes including the CCR5-Delta 32 allele were differentially transmitted from heterozygous parents to affected children. However, the magnitude of the reduced risk of KD associated with the CCR5-Delta 32 allele and certain CCR5 haplotypes was significantly greater in individuals who also possessed a high copy number of the gene encoding CCL3L1, the most potent CCR5 ligand. These findings, derived from the largest genetic study of any systemic vasculitis, suggest a central role of CCR5-CCL3L1 gene-gene interactions in KD susceptibility and the importance of gene modifiers in infectious diseases.