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Background  The etiology of Kawasaki Disease (KD) is enigmatic, although an infectious cause is suspected. Polymorphisms in CC chemokine receptor 5 (CCR5) and/or its potent ligand CCL3L1 influence KD susceptibility in US, European and Korean populations. However, the influence of these variations on KD susceptibility, coronary artery lesions (CAL) and response to intravenous immunoglobulin (IVIG) in Japanese children, who have the highest incidence of KD, is unknown.    Methodology/Principal Findings  We used unconditional logistic regression analyses to determine the associations of the copy number of the  CCL3L1  gene-containing duplication and  CCR2-CCR5  haplotypes in 133 Japanese KD cases [33 with CAL and 25 with resistance to IVIG] and 312 Japanese controls without a history of KD. We observed that the deviation from the population average of four  CCL3L1  copies (i.e., < or > four copies) was associated with an increased risk of KD and IVIG resistance (adjusted odds ratio (OR)  = 2.25, p = 0.004 and OR = 6.26, p = 0.089, respectively). Heterozygosity for the  CCR5  HHF*2 haplotype was associated with a reduced risk of both IVIG resistance (OR = 0.21, p = 0.026) and CAL development (OR = 0.44, p = 0.071).    Conclusions/Significance  The  CCL3L1-CCR5  axis may play an important role in KD pathogenesis. In addition to clinical and laboratory parameters, genetic markers may also predict risk of CAL and resistance to IVIG.

Association of CCR2-CCR5 Haplotypes and CCL3L1 Copy Number with Kawasaki Disease, Coronary Artery Lesions, and IVIG Responses in Japanese Children