Identification of B-cell-related HSPG2 and CDSN as susceptibility loci for Kawasaki disease

Kawasaki disease (KD) is an acute pediatric vasculitis that predominantly affects children under the age of 5 years. To date, genome-wide association studies (GWAS) have identified several KD susceptibility genes (e.g., BLK, CD40, FCGR2A, BCL2L11, and IGHV), which are mainly involved in B cell immunity. In this study, we aimed to identify additional KD susceptibility genes mainly involved in B cell development and functions by analyzing our previous GWAS data and conducting a replication study using new sample. Initially, we selected 30 single nucleotide polymorphisms (SNPs) in B-cell-related genes that were significantly (P < 0.01) associated with KD in our previous GWAS analysis of 247 KD cases with complete type and 1,000 healthy controls. Replication study was performed by genotyping the new 837 KD case samples with Fluidigm system and comparing them with 3,553 control genotypes. Among the 30 candidate SNPs, two were significantly associated with KD (P < 0.001) in the replication study. An even greater association between these SNPs and KD was observed in the combined analysis of GWAS and replication samples: odds ratio (OR) = 1.97 (P = 8.61 × 10⁻⁶) for rs2270699 (nonsynonymous SNP: c.10588C > T, p.Arg3530Trp) in the heparan sulfate proteoglycan 2 (HSPG2) gene and OR = 1.28 (P = 1.34 × 10⁻⁶) for rs3130992 (intronic SNP) in both the corneodesmosin (CDSN) and psoriasis susceptibility 1 candidate 1 (PSORS1C1) genes. These results suggest that the B-cell-related genes, HSPG2 and CDSN or PSORS1C1, play a role in the development of KD.