FNDC1 Polymorphism (rs3003174 C > T) Increased the Incidence of Coronary Artery Aneurysm in Patients with Kawasaki Disease in a Southern Chinese Population

Kun Lin; Linyuan Zhang; Yishuai Wang; Jinqing Li; Yufen Xu; Di Che; Hanran Mai; Hongyan Yu; Lanyan Fu; Bing Wei; Zhiyong Jiang; Lei Pi; Xiaoqiong Gu

doi:10.2147/JIR.S311956

FNDC1 Polymorphism (rs3003174 C > T) Increased the Incidence of Coronary Artery Aneurysm in Patients with Kawasaki Disease in a Southern Chinese Population

J Inflamm Res. 2021 Jun 21:14:2633-2640. doi: 10.2147/JIR.S311956. eCollection 2021.

Authors

Kun Lin^#^{1

2}, Linyuan Zhang^#^{1

2}, Yishuai Wang^#^{1

2

3}, Jinqing Li¹, Yufen Xu¹, Di Che¹, Hanran Mai⁴, Hongyan Yu¹, Lanyan Fu¹, Bing Wei², Zhiyong Jiang², Lei Pi¹, Xiaoqiong Gu^{1

2}

Affiliations

¹ Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510623, People's Republic of China.
² Department of Blood Transfusion and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510623, People's Republic of China.
³ School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510006, People's Republic of China.
⁴ Department of Andrology, Guangzhou Women and Children's Medical Center. Guangzhou Medical University, Guangzhou, Guangdong, 510623, People's Republic of China.

^# Contributed equally.

Abstract

Background: A large number of studies demonstrated that the key to the occurrence and development of Kawasaki disease (KD) is the over-activation of immune cells and the generation of various inflammatory factors, leading to the imbalance of the immune system. Recently, mutations in the FNDC1 gene have been shown to be associated with inflammatory responses. However, there have been no reports on the relationship between FNDC1 gene and KD so far.

Methods: We enrolled 1611 controls and 1459 patients with KD, including 372 patients with coronary artery aneurysm (CAA) and 179 patients with coronary artery lesion (CAL). The relationship between FNDC1 rs3003174 polymorphism and KD with CAA or without CAA was investigated.

Results: This study showed no evidence that the association between FNDC1 rs3003174 C>T polymorphism and KD susceptibility was statistically significant (CT versus CC: adjusted odds ratio (OR) =0.897, 95% confidence interval (CI) =0.769-1.045, P=0.162; TT versus CC: adjusted OR=0.995, 95% CI=0.786-1.260, P=0.968; dominant model: adjusted OR=0.916, 95% CI=0.792-1.059, P=0.235; and recessive model: adjusted OR=1.055, 95% CI=0.845-1.316, P=0.638). However, our further stratified analysis in the control and KD group bore out that the incidence of TT genotype of FNDC1 rs3003174 C > T polymorphism was higher than that of CC/CT genotype in KD patients stratified by CAA (adjusted OR=1.437, 95% CI=1.034-1.996, P=0.031). Moreover, a stratified analysis of age and gender in KD patients indicated that the rs3003174 TT genotype increased the risk of CAA formation in aged ≦60 months (CC/CT vs TT: adjusted OR=1.580, 95% CI=1.106-2.259, P=0.012) and male (CC/CT vs TT: adjusted OR=1.653, 95% CI=1.101-2.481, P=0.015) KD patients.

Conclusion: The results of this study demonstrated that the FNDC1 rs3003174 C>T polymorphism may be a hazard factor in the formation of CAA in KD patients that was not disclosed before.

Keywords: Kawasaki disease; coronary artery aneurysm; fibronectin type III domain containing 1; polymorphisms.

Grants and funding

This study was funded by the Guangdong Natural Science Fund, China (grant numbers 2019A1515012061, 2021A1515011207), the Guangzhou Science and Technology Program Project, China (grant numbers 201904010486, 202102010197), and the Guangzhou Institute of Pediatrics/Guangzhou Women and Children’s Medical Center Fund, China (Grant Number: GCP-2019-003, GCP-2019-006, and YIP-2019-050).