Identification of the TIFAB Gene as a Susceptibility Locus for Coronary Artery Aneurysm in Patients with Kawasaki Disease
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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.
KeywordsKawasaki disease Coronary artery aneurysm TRAF-interacting protein with FHA domain-containing protein B Single-nucleotide polymorphism Genome-wide association study
We thank all of our patients and their families for participating in this study. The following authors also participated in this study as members of the Korean Kawasaki Disease Genetics Consortium: In-Sook Park, Soo-Jong Hong, and Kwi-Joo Kim (Department of Pediatrics, Asan Medical Center, Seoul, Korea); Hyo-Kyoung Nam and Jung-Hye Byeon (Department of Pediatrics, Korea University Hospital, Seoul, Korea); Jung-Woo Rhim (Department of Pediatrics, The Catholic University of Korea, St. Mary’s Hospital, Daejeon, Korea); Dong Soo Kim (Department of Pediatrics, Yonsei University College of Medicine, Severance Children’s Hospital, Seoul, Korea); and Jae-Moo Lee and Jong-Duk Kim (Seoul Clinical Laboratories, Seoul, Korea). This study was supported by a Grant from the Ministry of Health and Welfare of the Republic of Korea (HI15C1575).
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Conflict of interest
The authors have no conflict of interest to declare.
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