TY - JOUR
T1 - Genome-wide association study identifies novel susceptibility genes associated with coronary artery aneurysm formation in Kawasaki disease
AU - Kuo, Ho Chang
AU - Li, Sung Chou
AU - Guo, Mindy Ming Huey
AU - Huang, Ying Hsien
AU - Yu, Hong Ren
AU - Huang, Fu Chen
AU - Jiao, Fuyong
AU - Kuo, Hsing Chun
AU - Andrade, Jorge
AU - Chan, Wen Ching
N1 - 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.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84969883877&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0154943
DO - 10.1371/journal.pone.0154943
M3 - 文章
C2 - 27171184
AN - SCOPUS:84969883877
SN - 1932-6203
VL - 11
JO - PLoS ONE
JF - PLoS ONE
IS - 5
M1 - e0154943
ER -