title: HLA class III genes involvement in Kawasaki disease: a case-control study in Caucasian population.
abstract: Kawasaki disease (KD) is an acute, multisystemic, febrile vasculitis of unknown aetiology, which affects young children mainly under 5 years of age. The clinical variability has until now prevented to decrypt KD aetiological factors. Recently, the importance of genetics and the pivotal role of the immune system have emerged. To investigate in this direction, genomic DNA from 74 Caucasian KD cases and 440 healthy controls has been analysed to characterize functional polymorphisms of relevant HLA class III genes: AGER -429 and -374, TNF -857, -308 and -238, HSPA1A +190, HSPA1B +1267 and HSPA1L +2437. Allele, genotype and haplotype frequencies were therefore compared with the chi-squared test and Fisher's exact test. Our data showed significant deviations between patients with Kawasaki disease and controls concerning the TNF -308 polymorphism genotype (GG: P = 0.0449) and allele (G,A: P = 0.0433) and -238 polymorphism genotype frequencies (AA: P = 0.0351). Moreover, we found differences concerning the HSPA1A +190 polymorphism (GC: P = 0.0317) and the HSPA1L +2437 polymorphism (TT: P = 0.0072; TC: P = 0.0250; T: P = 0.0037; C: P = 0.0037). The calculation of TNF -238 and HSPA1L haplotype frequencies also pointed out a statistically significant decrease in patients of CG haplotype (P = 0.0001), which could have a role in protecting from the inflammatory processes that characterize the disease progression. The results obtained point to a possible involvement of the entire HLA class III region in KD susceptibility.
authors.affiliation: Laboratory of Immunogenetics, Department of Biology & Biotechnology "L.Spallanzani", University of Pavia, Pavia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Maggioli
authors.forename: Chiara
authors.initials: C
authors.lastname: Boiocchi
authors.forename: Michele
authors.initials: M
authors.lastname: Zorzetto
authors.forename: Savina
authors.initials: S
authors.lastname: Mannarino
authors.forename: Grazia
authors.initials: G
authors.lastname: Bossi
authors.forename: Mariaclara
authors.initials: M
authors.lastname: Cuccia
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007223:Infant; D015810:Linkage Disequilibrium; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D018840:HSP70 Heat-Shock Proteins; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha