Association of CCR2-CCR5 haplotypes and CCL3L1 copy number with Kawasaki Disease, coronary artery lesions, and IVIG responses in Japanese children.
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.


RESULTS
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
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.
Mamtani
Manju
M
South Texas Veterans Health Care System and Department of Medicine, The Veterans Administration Center for AIDS and HIV-1 Infection, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
Matsubara
Tomoyo
T
Shimizu
Chisato
C
Furukawa
Susumu
S
Akagi
Teiji
T
Onouchi
Yoshihiro
Y
Hata
Akira
A
Fujino
Akihiro
A
He
Weijing
W
Ahuja
Sunil K
SK
Burns
Jane C
JC
D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D019742:Chemokines, CC / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology*; D056915:DNA Copy Number Variations / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007223:Infant; D016015:Logistic Models; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000188:drug therapy* / Q000235:genetics*; D019713:Receptors, CCR5 / Q000235:genetics*; D055815:Young Adult
C492767:CCL3L1 protein, human; D019742:Chemokines, CC; D016756:Immunoglobulins, Intravenous; D019713:Receptors, CCR5