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.

川崎病 (KD) 是一种急性小儿血管炎，主要影响 5 岁以下儿童。迄今为止，全基因组关联研究（GWAS）已鉴定出几个主要与B细胞免疫相关的KD易感基因（例如BLK、CD40、FCGR2A、BCL2L11和IGHV ）。在这项研究中，我们的目的是通过分析我们之前的 GWAS 数据并使用新样本进行复制研究，以确定主要参与 B 细胞发育和功能的其他 KD 易感基因。最初，我们在之前对 247 例完全型 KD 病例和 1,000 名健康对照进行 GWAS 分析时，选择了 B 细胞相关基因中 与 KD 显着相关（ P < 0.01）的 30 个单核苷酸多态性 (SNP)。通过使用 Fluidigm 系统对新的 837 个 KD 病例样本进行基因分型，并将其与 3,553 个对照基因型进行比较，进行了复制研究。 在重复研究中，30 个候选 SNP 中，有两个与 KD 显着相关（P < 0.001）。在 GWAS 和复制样本的联合分析中，观察到这些 SNP 和 KD 之间存在更大的关联：rs2270699 的比值比 (OR) = 1.97 ( P  = 8.61 × 10 ^-6 )（非同义 SNP：c.10588C > T，p硫酸乙酰肝素蛋白多糖 2 ( HSPG2 ) 基因中的 .Arg3530Trp) 以及角链蛋白 ( CDSN ) 和银屑病易感性 1 候选 1 ( PSORS1C1 ) 基因中 rs3130992 (内含子 SNP) 的OR = 1.28 ( P  = 1.34 × 10 ^{-6 )。}这些结果表明 B 细胞相关基因HSPG2和CDSN 或 PSORS1C1在 KD 的发生中发挥作用。