Genetic variants in NEBL (rs16921209, OR 32.22) and TUBA3C (rs17076896, OR 21.03) were significantly associated with the development of coronary artery aneurysms in patients with Kawasaki disease.
Case-Control (n=157)
No
This genome-wide association study identified novel susceptibility genes, including NEBL and TUBA3C, that are strongly associated with the formation of coronary artery aneurysms in patients with Kawasaki disease.
Odds Ratio: 32.22
p-value: p=7.44 × 10^-9
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.
Kuo et al. (Thu,) conducted a case-control in Kawasaki Disease (n=157). NEBL rs16921209 genetic variant vs. Absence of the genetic variant was evaluated on Coronary artery aneurysm (CAA) formation (OR 32.22, p=7.44 × 10^-9). Genetic variants in NEBL (rs16921209, OR 32.22) and TUBA3C (rs17076896, OR 21.03) were significantly associated with the development of coronary artery aneurysms in patients with Kawasaki disease.