title: Genetic susceptibility to Kawasaki disease: analysis of pattern recognition receptor genes.
abstract: Kawasaki disease (KD) is a systemic vasculitis of unknown etiology occurring in infants and children. Several lines of evidence suggested the importance of genetic factors and infectious triggers for the pathogenesis of KD. We have reported that oral administration of a pure NOD1 ligand induces coronary arteritis in mice without fail. Since NOD1 is one of the pattern recognition receptors (PRRs) which play important roles in the innate immunity for the detection of microbial substances and induce inflammatory responses, we have investigated the association of PRR genes with the development of KD. Forty-six tagging-SNPs in 19 PRR genes were genotyped in Japanese KD patients (n=356, consisting of two groups) and controls (n=215). The genotypes and allele frequencies of each SNP or haplotype were compared between KD patients and controls. As a result, we did not find any genes with strongly contributed to the development of KD. A haplotype, G-T-C-C, in the NOD1 gene, was associated with lower risk for KD development (KD 1st group versus controls: 23.2% versus 35.3%, Pc=0.0385). The second-round case-control study in KD group 2 demonstrated that a haplotype, T-T-C-G-A-C, in the NLRP1 gene was associated with a higher risk for KD development (4.9% versus 1.2%, Pc=0.035). From the association analysis of SNPs and haplotypes of 19 PRR genes, NOD1 and NLRP1 seemed to partly contribute to the development of KD. Further analysis with larger samples of another independent set would be needed to find confirmative results.
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Sagano
authors.initials: S
authors.lastname: Onoyama
authors.forename: Kenji
authors.initials: K
authors.lastname: Ihara
authors.forename: Yui
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ikeda
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Yamamura
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hoshina
authors.forename: Yumi
authors.initials: Y
authors.lastname: Mizuno
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hara
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000293:Adolescent; D000483:Alleles; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000235:genetics* / Q000276:immunology; D000070576:NLR Proteins; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000070576:NLR Proteins; C427903:NLRP1 protein, human; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein