Genomics & Informatics

Korea Genome Organization (한국유전체학회)
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Identification of LEF1 as a Susceptibility Locus for Kawasaki Disease in Patients Younger than 6 Months of Age

  • Kim, Hea-Ji (Asan Institute for Life Sciences, University of Ulsan College of Medicine) ;
  • Yun, Sin Weon (Department of Pediatrics, Chung-Ang University Hospital) ;
  • Yu, Jeong Jin (Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Yoon, Kyung Lim (Department of Pediatrics, Kyung Hee University Hospital at Gangdong) ;
  • Lee, Kyung-Yil (Department of Pediatrics, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Kil, Hong-Ryang (Department of Pediatrics, Chungnam National University Hospital) ;
  • Kim, Gi Beom (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Han, Myung-Ki (Department of Pediatrics, Gangneung Asan Hospital, University of Ulsan College of Medicine) ;
  • Song, Min Seob (Department of Pediatrics, Inje University Busan Paik Hospital) ;
  • Lee, Hyoung Doo (Department of Pediatrics, Pusan National University Hospital) ;
  • Ha, Kee Soo (Department of Pediatrics, Korea University Ansan Hospital) ;
  • Sohn, Sejung (Department of Pediatrics, Ewha Womans University Hospital) ;
  • Ebata, Ryota (Department of Pediatrics, Chiba-University Graduate School of Medicine) ;
  • Hamada, Hiromichi (Department of Pediatrics, Tokyo Women's Medical University Yachivo Medical Center) ;
  • Suzuki, Hiroyuki (Department of Pediatrics, Wakayama Medical University) ;
  • Kamatani, Yoichiro (Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences) ;
  • Kubo, Michiaki (Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences) ;
  • Ito, Kaoru (Laboratory for Cardiovascular Diseases, RIKEN Center for Integrative Medical Sciences) ;
  • Onouchi, Yoshihiro (Laboratory for Cardiovascular Diseases, RIKEN Center for Integrative Medical Sciences) ;
  • Hong, Young Mi (Department of Pediatrics, Ewha Womans University Hospital) ;
  • Jang, Gi Young (Department of Pediatrics, Korea University Ansan Hospital) ;
  • Lee, Jong-Keuk (Asan Institute for Life Sciences, University of Ulsan College of Medicine) ;
  • The Korean Kawasaki Disease Genetics Consortium (The Korean Kawasaki Disease Genetics Consortium)
  • Received : 2018.03.23
  • Accepted : 2018.04.11
  • Published : 2018.06.30
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Abstract

Kawasaki disease (KD) is an acute febrile vasculitis predominately affecting infants and children. The dominant incidence age of KD is from 6 months to 5 years of age, and the incidence is unusual in those younger than 6 months and older than 5 years of age. We tried to identify genetic variants specifically associated with KD in patients younger than 6 months or older than 5 years of age. We performed an age-stratified genome-wide association study using the Illumina HumanOmni1-Quad BeadChip data (296 cases vs. 1,000 controls) and a replication study (1,360 cases vs. 3,553 controls) in the Korean population. Among 26 candidate single nucleotide polymorphisms (SNPs) tested in replication study, only a rare nonsynonymous SNP (rs4365796: c.1106C>T, p.Thr369Met) in the lymphoid enhancer binding factor 1 (LEF1) gene was very significantly associated with KD in patients younger than 6 months of age (odds ratio [OR], 3.07; $p_{combined}=1.10{\times}10^{-5}$), whereas no association of the same SNP was observed in any other age group of KD patients. The same SNP (rs4365796) in the LEF1 gene showed the same direction of risk effect in Japanese KD patients younger than 6 months of age, although the effect was not statistically significant (OR, 1.42; p = 0.397). This result indicates that the LEF1 gene may play an important role as a susceptibility gene specifically affecting KD patients younger than 6 months of age.

Keywords

References

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