Recent advances in research on gene polymorphisms in Kawasaki disease

Table 1 Genetic polymorphisms linked to susceptibility and complications of Kawasaki disease

Gene	SNP/Locus	Variant	Functional impact	Association with KD	Population-specific risk	Ref.
ITPKC	rs28493229	C→T	Downregulates gene expression, impairing immune regulation; affects mRNA stability/splicing	Increased susceptibility to KD and risk of CALs	Significant in both Asian and Caucasian populations	[10]
CASP3	rs113420705	G→A	Alters inflammatory cytokine clearance during apoptosis, leading to sustained inflammation	Correlated with KD severity and CALs development	Strongest association in East Asian cohorts	[11]
CD40	rs153045	T→C	Enhances T-cell/B-cell activation and macrophage-mediated inflammation via CD40-CD40L interaction	T-allele is linked to higher KD susceptibility (Asian populations); there is no significant association in North Indian populations	Ethnic variability (Asian-specific)	[12,13]
HLA	HLA-B51, HLA-C03	–	Triggers aberrant immune responses against the vascular endothelium via HLA-mediated antigen presentation	Strongly associated with KD onset and CALs (e.g., Japanese cohort)	Highly population-dependent (HLA diversity)	[14]
FCGR2A	rs1801274	A→G	Modulates IgG receptor affinity, impairing immune complex clearance	Predicts IVIG resistance and CALs progression	Pediatric KD patients (global, with varying effect sizes)	[15,16]

¹Functional impact: ITPKC and CASP3 variants disrupt immune homeostasis, promoting CALs; FCGR2A polymorphism affects intravenous high-dose immunoglobulin efficacy via Fcγ receptor modulation; HLA alleles contribute to population-specific Kawasaki disease risk due to MHC diversity.

Clinical implications: Biomarker potential: ITPKC, CASP3, and FCGR2A may predict CALs or IVIG resistance; Therapeutic targeting: CD40 and HLA pathways could inform personalized immunomodulatory strategies.

Population heterogeneity: Asian populations show stronger associations for ITPKC, CASP3, and CD40; HLA and FCGR2A effects vary by ancestry, underscoring the need for diverse genetic studies.

CAL: Coronary artery lesions; IVIG: Intravenous high-dose immunoglobulin; KD: Kawasaki disease.