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Pediatric Cardiology

, Volume 40, Issue 3, pp 483–488 | Cite as

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

  • Young-Chang Kwon
  • Jae-Jung Kim
  • Jeong Jin Yu
  • Sin Weon Yun
  • Kyung Lim Yoon
  • Kyung-Yil Lee
  • Hong-Ryang Kil
  • Gi Beom Kim
  • Myung-Ki Han
  • Min Seob Song
  • Hyoung Doo Lee
  • Kee Soo Ha
  • Sejung Sohn
  • Young Mi Hong
  • Gi Young Jang
  • Jong-Keuk LeeEmail author
  • Korean Kawasaki Disease Genetics Consortium
Original Article
  • 140 Downloads

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

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

Notes

Acknowledgements

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).

Compliance with Ethical Standards

Conflict of interest

The authors have no conflict of interest to declare.

Supplementary material

246_2018_1992_MOESM1_ESM.docx (83 kb)
Supplementary material 1 (DOCX 83 KB)
246_2018_1992_MOESM2_ESM.docx (73 kb)
Supplementary material 2 (DOCX 72 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Young-Chang Kwon
    • 1
  • Jae-Jung Kim
    • 1
  • Jeong Jin Yu
    • 2
  • Sin Weon Yun
    • 3
  • Kyung Lim Yoon
    • 4
  • Kyung-Yil Lee
    • 5
  • Hong-Ryang Kil
    • 6
  • Gi Beom Kim
    • 7
  • Myung-Ki Han
    • 8
  • Min Seob Song
    • 9
  • Hyoung Doo Lee
    • 10
  • Kee Soo Ha
    • 11
  • Sejung Sohn
    • 12
  • Young Mi Hong
    • 12
  • Gi Young Jang
    • 11
  • Jong-Keuk Lee
    • 1
    Email author
  • Korean Kawasaki Disease Genetics Consortium
  1. 1.Asan Institute for Life Sciences, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulSouth Korea
  2. 2.Department of Pediatrics, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulSouth Korea
  3. 3.Department of PediatricsChung-Ang University HospitalSeoulSouth Korea
  4. 4.Department of PediatricsKyung Hee University Hospital at GangdongSeoulSouth Korea
  5. 5.Department of Pediatrics, Daejeon St. Mary’s HospitalThe Catholic University of KoreaDaejeonSouth Korea
  6. 6.Department of PediatricsChungnam National University HospitalDaejeonSouth Korea
  7. 7.Department of PediatricsSeoul National University Children’s HospitalSeoulSouth Korea
  8. 8.Department of Pediatrics, Gangneung Asan HospitalUniversity of UlsanGangneungSouth Korea
  9. 9.Department of PediatricsInje University Paik HospitalBusanSouth Korea
  10. 10.Department of PediatricsPusan National University HospitalBusanSouth Korea
  11. 11.Department of PediatricsKorea University HospitalSeoulSouth Korea
  12. 12.Department of PediatricsEwha Womans University HospitalSeoulSouth Korea

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