Associations of Mitochondrial Variants With Lipidomic Traits in a Chinese Cohort With Coronary Artery Disease

Zixian Wang; Hui Chen; Min Qin; Chen Liu; Qilin Ma; Xiaoping Chen; Ying Zhang; Weihua Lai; Xiaojuan Zhang; Shilong Zhong

doi:10.3389/fgene.2021.630359

Associations of Mitochondrial Variants With Lipidomic Traits in a Chinese Cohort With Coronary Artery Disease

Front Genet. 2021 Mar 25:12:630359. doi: 10.3389/fgene.2021.630359. eCollection 2021.

Authors

Zixian Wang^{1

2

3

4}, Hui Chen^{1

2

3}, Min Qin^{1

2

3}, Chen Liu⁵, Qilin Ma⁶, Xiaoping Chen⁷, Ying Zhang⁸, Weihua Lai², Xiaojuan Zhang², Shilong Zhong^{1

2

3

4}

Affiliations

¹ Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, China.
² Department of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
³ Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
⁴ School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China.
⁵ Department of Cardiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
⁶ Department of Cardiology, Xiangya Hospital, Central South University, Changsha, China.
⁷ Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.
⁸ Department of Cardiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Abstract

Plasma lipids have been at the center stage of the prediction and prevention strategies for cardiovascular diseases (CVDs), and novel lipidomic traits have been recognized as reliable biomarkers for CVD risk prediction. The mitochondria serve as energy supply sites for cells and can synthesize a variety of lipids autonomously. Therefore, investigating the relationships between mitochondrial single nucleotide polymorphism (SNPs) and plasma lipidomic traits is meaningful. Here, we enrolled a total of 1,409 Han Chinese patients with coronary artery disease from three centers and performed linear regression analyses on the SNPs of mitochondrial DNA (mtDNA) and lipidomic traits in two independent groups. Sex, age, aspartate aminotransferase, estimated glomerular filtration rate, antihypertensive drugs, hypertension, and diabetes were adjusted. We identified three associations, namely, D-loop _m.16089T>C with TG(50:4) NL-16:0, D-loop _m.16145G>A with TG(54:5) NL-18:0, and D-loop _m.16089T>C with PC(16:0_16:1) at the statistically significant threshold of FDR < 0.05. Then, we explored the relationships between mitochondrial genetic variants and traditional lipids, including triglyceride, total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), and high-density lipoprotein cholesterol. Two significant associations were found, namely MT-ND6 _m.14178T>C with TC and D-loop _m.215A>G with LDLC. Furthermore, we performed linear regression analysis to determine on the SNPs of mtDNA and left ventricular ejection fraction (LVEF) and found that the SNP D-loop _m.16145G>A was nominally significantly associated with LVEF (P = 0.047). Our findings provide insights into the lipidomic context of mtDNA variations and highlight the importance of studying mitochondrial genetic variants related to lipid species.

Keywords: association analyses; coronary artery disease; lipidomic; mitochondrial DNA; polymorphisms.