Polymorphisms in chemokine receptor genes and susceptibility to Kawasaki disease.
Kawasaki disease (KD) is an acute vasculitis occurring in young children. Its aetiology is unknown, but an infectious agent is assumed. Increased levels of proinflammatory cytokines and chemokines have been reported in KD. Genetic variation in these genes and the receptors for these genes could influence the regulation of cytokines and chemokines. In a case-control study of 170 Dutch Caucasian KD patients and 300 healthy Dutch Caucasian controls, common genetic variants in chemokine receptor genes CCR3, CCR2, CCR5, CX3CR1, CXCR1 and CXCR2 were analysed. Of the eight studied single nucleotide polymorphisms (SNPs) in the CCR3-CCR2-CCR5 gene cluster, four showed a significant association with susceptibility to KD. Moreover the CCR5-Delta32 was observed with an allele frequency of 10.7% in the control population compared to 6.5% in the KD patients (P = 0.04). Two haplotypes of the CCR3-CCR2-CCR5 gene-cluster appear to be at risk haplotypes for KD and one a protective haplotype. No association was observed with the studied SNPs in CX3CR1, CXCR1 and CXCR2. In conclusion, in a Dutch cohort of KD patients an association of KD occurrence with common genetic variants in the chemokine receptor gene-cluster CCR3-CCR2-CCR5 was observed.
Emma Children's Hospital, Academic Medical Center (AMC), Amsterdam, The Netherlands. w.b.breunis@amc.uva.nl
W B
WB
Breunis
M H
MH
Biezeveld
J
J
Geissler
I M
IM
Kuipers
J
J
Lam
J
J
Ottenkamp
A
A
Hutchinson
R
R
Welch
S J
SJ
Chanock
T W
TW
Kuijpers
D016022:Case-Control Studies; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D009080:Mucocutaneous Lymph Node Syndrome / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054390:Receptors, CCR2; D054397:Receptors, CCR3; D019713:Receptors, CCR5 / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics*
C515334:CCR2 protein, human; C515350:CCR3 protein, human; D054390:Receptors, CCR2; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019707:Receptors, Chemokine