Assessment of the Clinical Heterogeneity of Kawasaki Disease Using Genetic Variants of and .

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 (; rs6993775) and Fc gamma receptor II a (; rs1801274) in a large number of case (n=1,011) and control (n=4,533) samples.

RESULTS

and were very significantly associated with KD in Korean KD patients (odds ratio [OR],1.48; p=4.63×10⁻¹¹ for , and OR, 1.26; p=1.42×10⁻⁴ for ). However, in KD subgroup analysis, we found that neither nor were 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 was associated with all KD subgroups, whereas was 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.