Korean Circ J.  2019 Jan;49(1):99-108. 10.4070/kcj.2018.0224.

Assessment of the Clinical Heterogeneity of Kawasaki Disease Using Genetic Variants of BLK and FCGR2A

• Sim BK
• Park H
• Kim JJ
• Yun SW
• Yu JJ
• Yoon KL
• Lee KY
• Kil HR
• Kim GB
• Han MK
• Song MS
• Lee HD
• Ha KS
• Sohn S
• Hong YM
• Jang GY
• Lee JK
• on behalf of the Korean Kawasaki Disease Genetics Consortium

• KMID: 2430753
• DOI: http://doi.org/10.4070/kcj.2018.0224

Abstract

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
BLK and FCGR2A were 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 BLK nor FCGR2A 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 BLK was associated with all KD subgroups, whereas FCGR2A 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.

Keyword

Mucocutaneous lymph node syndrome; Genome-wide association study; Polymorphism, single nucleotide

MeSH Terms

Biomarkers
Diagnosis
Genetic Heterogeneity
Genome-Wide Association Study
Humans
Male
Mucocutaneous Lymph Node Syndrome*
Polymorphism, Single Nucleotide
Population Characteristics*
Protein-Tyrosine Kinases
Biomarkers
Protein-Tyrosine Kinases

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