Format

Send to

Choose Destination
Pediatr Cardiol. 2019 Mar;40(3):483-488. doi: 10.1007/s00246-018-1992-7. Epub 2018 Sep 28.

Identification of the TIFAB Gene as a Susceptibility Locus for Coronary Artery Aneurysm in Patients with Kawasaki Disease.

Author information

1
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, South Korea.
2
Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
3
Department of Pediatrics, Chung-Ang University Hospital, Seoul, South Korea.
4
Department of Pediatrics, Kyung Hee University Hospital at Gangdong, Seoul, South Korea.
5
Department of Pediatrics, Daejeon St. Mary's Hospital, The Catholic University of Korea, Daejeon, South Korea.
6
Department of Pediatrics, Chungnam National University Hospital, Daejeon, South Korea.
7
Department of Pediatrics, Seoul National University Children's Hospital, Seoul, South Korea.
8
Department of Pediatrics, Gangneung Asan Hospital, University of Ulsan, Gangneung, South Korea.
9
Department of Pediatrics, Inje University Paik Hospital, Busan, South Korea.
10
Department of Pediatrics, Pusan National University Hospital, Busan, South Korea.
11
Department of Pediatrics, Korea University Hospital, Seoul, South Korea.
12
Department of Pediatrics, Ewha Womans University Hospital, Seoul, South Korea.
13
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, South Korea. cookie_jklee@hotmail.com.

Abstract

Kawasaki disease (KD) is a self-limiting systemic vasculitis of unknown etiology. KD is often complicated by coronary artery aneurysms (CAAs), which develop in about 20-25% of untreated children and 3-5% of children treated with intravenous immunoglobulin therapy. To identify the risk loci for CAA susceptibility in patients with KD, we performed a genome-wide association study (GWAS) using our previous Illumina HumanOmni1-Quad BeadChip data (296 KD patients) and a new replication study in an independent sample set (713 KD patients) by grouping KD patients without CAA (control) versus KD patients with extremely large aneurysms (diameter ≥ 5 mm) (case). Among 44 candidate single -nucleotide polymorphisms (SNPs) selected from the initial GWAS data (33 cases vs. 215 controls), a SNP (rs899162) located 7 kb upstream of the TIFAB gene on chromosome five was replicated in an independent sample (12 cases vs. 532 controls). In the combined analysis (45 cases vs. 747 controls), the SNP (rs899162) showed a highly significant association with CAA formation (diameter ≥ 5 mm) in patients with KD (odds ratio = 3.20, 95% confidence interval = 2.02-5.05, Pcombined = 1.95 × 10-7). These results indicate that the TIFAB gene may act as a CAA susceptibility locus in patients with KD.

KEYWORDS:

Coronary artery aneurysm; Genome-wide association study; Kawasaki disease; Single-nucleotide polymorphism; TRAF-interacting protein with FHA domain-containing protein B

PMID:
30267110
DOI:
10.1007/s00246-018-1992-7
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center