Polymorphisms in chemokine receptor genes and susceptibility to Kawasaki disease

Abstract

SummaryKawasaki 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-D32 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.

Susceptibility genes for Kawasaki disease: toward implementation of personalized medicine

“…30 Although several other groups have studied other combinations of HLA subtypes, no consistent association has been detected so far. Considering that no significant linkage was detected near the 6p region in our genome-wide linkage analysis, 31 34 and MCP-1 35 ), hematopoietins (interleukin-4 (IL-4) [36][37][38] and IL-6 39 ), IL-1 family (IL-1b, 37 IL-18, 40 and IL-1Ra 37 ), IL-10 family (IL-10 41 ), platelet-derived growth factor family (vascular endothelial growth factor (VEGF) [42][43][44][45] and VEGFR2 42 ), and tumor necrosis factor (TNF) family (TNF-a, 46-50 lipoteichoic acid, 47 and CD40L 51,52 ). Other candidates include plasma proteins (C-reactive protein [53][54][55] and MBL2 53,55,56 ), matrix metalloproteinase (MMP) and their inhibitors (MMP2, 58 MMP3, 57,58 MMP-9, 58 MMP-12, 58 MMP-13, 58 and tissue inhibitors of metalloproteinase-2 59 ), enzymes related to atherosclerosis (methylenetetrahydrofolate reductase (MTHFR), 60 endothelial nitric oxide synthase, 61 and inducible nitric oxide synthase 61 ), components of the renin-angiotensin system (angiotensin-converting enzyme [62][63][64][65] and AGTR1 64 ), and an unclassified group (CD14, 66 FCGR2A, 67,68 SLC11A1, 69 PLA2G7, 70 UGT1A1, 71 MICA, 72 and HMOX1 71 ).…”

Polymorphisms in the promoter regions of the CXCL1 and CXCL2 genes contribute to increased risk of alopecia areata in the Korean population

“…Previous studies have reported an association between the SNPs occurring in chemokine genes and autoimmune diseases, including systemic lupus erythematosus (SLE) (Brown et al, 2007;Im et al, 2014), Sjögren syndrome (Kahlmann et al, 2007), Kawasaki disease (KD) (Breunis et al, 2007;Jhang et al, 2009), and rheumatoid arthritis (RA) (Zapico et al, 2000;Teng et al, 2012). Brown et al (2007) revealed that the G allele of the -2518A/G SNP in the CCL2 gene significantly increased the risk of SLE among Caucasians, but not among African Americans (P < 0.0001).…”

Schutzimpfung gegen Rotavirusgastroenteritis

“…Ein Polymorphismus im CCChemo kinrezeptor 5 (CCR5) und/oder seinem Liganden CCL3L1 scheint die Suszeptibi lität für KS zu beeinflussen, so gibt es Hin weise darauf, dass die Rekrutierung von Entzündungszellen beim KS durch CCR5 vermittelt werden könnte [4,5,17]. Abge sehen vom hohen Vorkommen der CCR5 δ32Deletion in vielen nordeuropäischen Ländern und besonders in Dänemark [5,26] gibt es keine plausiblen Erklärungen für die Inzidenzunterschiede innerhalb der europäischen Länder sowie zwischen Europa und den USA.…”