Korean Circulation Journal

The Korean Society of Cardiology (대한심장학회)
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Sex-Specific Susceptibility Loci Associated With Coronary Artery Aneurysms in Patients With Kawasaki Disease

  • Jae-Jung Kim (Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Young Mi Hong (Department of Pediatrics, Ewha Womans University Hospital) ;
  • Sin Weon Yun (Department of Pediatrics, Chung-Ang University Hospital) ;
  • Kyung-Yil Lee (Department of Pediatrics, Daejeon St. Mary's Hospital, The Catholic University of Korea) ;
  • Kyung Lim Yoon (Department of Pediatrics, Kyung Hee University Hospital at Gangdong) ;
  • Myung-Ki Han (Department of Pediatrics, Gangneung Asan Hospital, University of Ulsan) ;
  • Gi Beom Kim (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Hong-Ryang Kil (Department of Pediatrics, Chungnam National University Hospital) ;
  • Min Seob Song (Department of Pediatrics, Inje University Paik Hospital) ;
  • Hyoung Doo Lee (Department of Pediatrics, Pusan National University Hospital) ;
  • Kee Soo Ha (Department of Pediatrics, Korea University Guro Hospital) ;
  • Hyun Ok Jun (Department of Cardiovascular Surgery, Severance Cardiovascular Hospital, Yonsei University College of Medicine) ;
  • Jeong Jin Yu (Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Gi Young Jang (Department of Pediatrics, Korea University Ansan Hospital) ;
  • Jong-Keuk Lee (Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Korean Kawasaki Disease Genetics Consortium (Korean Kawasaki Disease Genetics Consortium)
  • Received : 2023.08.28
  • Accepted : 2024.02.26
  • Published : 2024.09.01
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Abstract

Background and Objectives: Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20-25% of untreated children with KD and 3-5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients. Methods: A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases). Results: Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25-9.98; p=0.00204-1.96×10-6), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD. Conclusions: A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.

Keywords

Acknowledgement

We thank all our patients and their families for participating in this study.

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