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Genomics Inform. 2018 Jun;16(2):36-41. doi: 10.5808/GI.2018.16.2.36. Epub 2018 Jun 30.

Identification of LEF1 as a Susceptibility Locus for Kawasaki Disease in Patients Younger than 6 Months of Age.

Author information

1
Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul 05505, Korea.
2
Department of Pediatrics, Chung-Ang University Hospital, Seoul 06973, Korea.
3
Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
4
Department of Pediatrics, Kyung Hee University Hospital at Gangdong, Seoul 05278, Korea.
5
Department of Pediatrics, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon 34943, Korea.
6
Department of Pediatrics, Chungnam National University Hospital, Daejeon 35015, Korea.
7
Department of Pediatrics, Seoul National University Children's Hospital, Seoul 03080, Korea.
8
Department of Pediatrics, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung 25440, Korea.
9
Department of Pediatrics, Inje University Busan Paik Hospital, Busan 47392, Korea.
10
Department of Pediatrics, Pusan National University Hospital, Busan 49241, Korea.
11
Department of Pediatrics, Korea University Ansan Hospital, Ansan 15355, Korea.
12
Department of Pediatrics, Ewha Womans University Hospital, Seoul 07985, Korea.
13
Department of Pediatrics, Chiba-University Graduate School of Medicine, Chiba 260-8670, Japan.
14
Department of Pediatrics, Tokyo Women's Medical University Yachivo Medical Center, Yachivo 276-8524, Japan.
15
Department of Pediatrics, Wakayama Medical University, Wakayama 641-8509, Japan.
16
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
17
Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
18
Laboratory for Cardiovascular Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.

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; pcombined = 1.10 × 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:

Kawasaki disease; genome-wide association study; lymphoid enhancer binding factor1 (LEF1); single nucleotide polymorphism

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