Assessment of the clinical heterogeneity of Kawasaki disease using genetic variants of BLK and FCGR2A

Background and Objectives: Patients with Kawasaki disease (KD) are clinically heterogeneous because its diagnosis is based solely on clinical observation and there are no definitive biomarkers. We dissected the clinical heterogeneity of KD patients using the KD-associated genetic variants. Methods: We performed a genetic association analysis in several KD subgroups categorized by clinical characteristics using the KD-associated variants of the B lymphoid tyrosine kinase (BLK; rs6993775) and Fc gamma receptor II a (FCGR2A; rs1801274) in a large number of case (n=1,011) and control (n=4,533) samples. Results: BLKand FCGR2Awere very significantly associated with KD in Korean KD patients (odds ratio [OR],1.48; p=4.63×10 ⁻¹¹ for BLK, and OR, 1.26; p=1.42×10 ⁻⁴ for FCGR2A). However, in KD subgroup analysis, we found that neither BLKnor FCGR2Awere associated with either incomplete Kawasaki disease (iKD) type patients or those older than 5 years of age (p>0.2), suggesting that patients with iKD or those older than 5 years of age are a unique subgroup of KD. In genetic association analysis after excluding iKD patients and those older than 5 years old, we found that BLKwas associated with all KD subgroups, whereas FCGR2Awas specifically associated with male KD patients younger than 1 year of age (OR, 2.22; p=2.35×10 ⁻⁵ ). Conclusions: KD is a clinically and genetically heterogeneous disease. These findings will provide new insights into the clinical and genetic heterogeneity of KD.