Genome-wide association study identifies novel susceptibility genes associated with coronary artery aneurysm formation in Kawasaki disease

Ho Chang Kuo, Sung Chou Li, Mindy Ming Huey Guo, Ying Hsien Huang, Hong Ren Yu, Fu Chen Huang, Fuyong Jiao, Hsing Chun Kuo, Jorge Andrade, Wen Ching Chan

研究成果: 期刊稿件文章同行評審

48 引文 斯高帕斯(Scopus)

摘要

Kawasaki disease (KD) or Kawasaki syndrome is known as a vasculitis of small to medium-sized vessels, and coronary arteries are predominantly involved in childhood. Generally, 20-25% of untreated with IVIG and 3-5% of treated KD patients have been developed coronary artery lesions (CALs), such as dilatation and aneurysm. Understanding how coronary artery aneurysms (CAAs) are established and maintained in KD patients is therefore of great importance. Upon our previous genotyping data of 157 valid KD subjects, a genome-wide association study (GWAS) has been conducted among 11 (7%) CAA-developed KD patients to reveal five significant genetic variants passed pre-defined thresholds and resulted in two novel susceptibility protein-coding genes, which are NEBL (rs16921209 (P = 7.44 × 10-9; OR = 32.22) and rs7922552 (P = 8.43 × 10-9; OR = 32.0)) and TUBA3C (rs17076896 (P = 8.04 × 10-9; OR = 21.03)). Their known functions have been reported to associate with cardiac muscle and tubulin, respectively. As a result, this might imply their putative roles of establishing CAAs during KD progression. Additionally, various model analyses have been utilized to determine dominant and recessive inheritance patterns of identified susceptibility mutations. Finally, all susceptibility genes hit by significant genetic variants were further investigated and the top three representative gene-ontology (GO) clusters were regulation of cell projection organization, neuron recognition, and peptidyl-threonine phosphorylation. Our results help to depict the potential routes of the pathogenesis of CAAs in KD patients and will facilitate researchers to improve the diagnosis and prognosis of KD in personalized medicine.

原文英語
文章編號e0154943
期刊PLoS ONE
11
發行號5
DOIs
出版狀態已出版 - 01 05 2016

文獻附註

Publisher Copyright:
© 2016 Kuo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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