Mitochondrial related variants associated with cardiovascular traits

Area of Science:

• Genetics and Molecular Biology
• Cardiovascular Research
• Mitochondrial Biology

Background:

• Cardiovascular disease (CVD) is a leading global cause of mortality, influenced by complex genetic, clinical, social, and environmental factors.
• While autosomal genetic variants are increasingly recognized, the etiology of many CVD cases remains unclear.
• Mitochondria play a critical role in CVD pathophysiology, with recent emphasis on mitochondrial DNA (mtDNA) variants and haplogroups.

Purpose of the Study:

• To investigate the association of genetic variants in both mtDNA and nuclear-encoded mitochondrial genes (NEMG) with CVD, coronary artery disease (CAD), hypertension, and serum lipids.
• To perform subgroup analysis for the influence of these variants in individuals with diabetes.
• To identify novel genetic markers related to CVD and its risk factors.

Main Methods:

• Analysis of 371,542 variants in 2,527 NEMG and 192 variants in 32 mitochondrial genes.
• Utilized data from 381,994 participants in the UK Biobank.
• Stratified analyses based on the presence or absence of diabetes.

Main Results:

• Mitochondrial variants were associated with CVD, hypertension, and serum lipids.
• Mitochondrial haplogroups J, T, and U showed significant associations with CAD and/or CVD.
• Variants in NOS3, TOMM40, SLC22A2, and HLA-DQA1 genes were linked to CVD, CAD, hypertension, blood pressure, and serum lipids.

Conclusions:

• Mitochondrial variants and haplogroups are relevant to CVD etiology.
• Mitochondrial haplogroup U is newly linked to CVD, and J and T associations are confirmed.
• NOS3, SLC22A2, TOMM40, and HLA-DQA1 genes represent potential common pathways in CVD, blood pressure, and lipid regulation, especially in diabetic contexts.