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

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-loopm.16089T>C with TG(50:4) NL-16:0, D-loopm.16145G>A with TG(54:5) NL-18:0, and D-loopm.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-ND6m.14178T>C with TC and D-loopm.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-loopm.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.