TY  - JOUR
T1  - Associations of Mitochondrial Heteroplasmy in Blood Monocytes with Its Phenotypic Indices and Cardiometabolic Parameters in Metabolic Syndrome: A Pilot Cross-sectional Study 
AU  - Voronova, Sophia
AU  - Bograya, Maria
AU  - Koshel, Anastasia
AU  - Malashchenko, Vladimir
AU  - Vulf, Maria
AU  - Beletskaya, Maria
AU  - Litvinova, Larisa
JF  - Gene Expression
VL  - 25
IS  - 2
SN  - 1555-3884
SP  - e00088
EP  - e00088
Y1  - 2026-04-30
DO  - 10.14218/GE.2025.00088
UR  - https://www.xiahepublishing.com/1555-3884/GE-2025-00088
AB  - Background and objectives 
Mitochondrial DNA (mtDNA) variability, especially heteroplasmy, is believed to affect cellular immunobiogenesis, particularly in monocytes in metabolic syndrome (MetS). This study aimed to identify associations of monocytic mtDNA variability with its phenotypic indices, including cytokine secretion and gene expression, and cardiometabolic parameters in patients with MetS.
Methods
The cross-sectional study recruited 87 adult participants, including 34 healthy blood donors (Control group), 21 obese patients (Obesity group), and 32 MetS patients (MetS group). Blood biochemistry tests were performed on venous blood samples, and monocytes (CD14+ cells) were isolated. Monocyte mtDNA was analyzed by next-generation sequencing to identify low (5–10%) and intermediate (10–95%) heteroplasmy, and homoplasmy (≥95%). Expression of genes related to mitochondrial biogenesis, mitochondrial uncoupling, oxidative stress system, and NF-κB signaling was assessed by quantitative real-time polymerase chain reaction. Monocytes cultured with and without lipopolysaccharide for 24 h were analyzed by enzyme-linked immunosorbent assay to assess the cytokine secretion stimulation index.
Results
Monocyte mtDNA showed low variability, but alternative homoplasmies were significantly more common. Intermediate and low heteroplasmy from the protein-coding locus correlated with stenosis (r = 0.396; 95% confidence interval (CI) 0.067–0.647) and low-density lipoprotein levels (r = −0.258; 95% CI −0.45 – −0.043). Intermediate heteroplasmy from the rRNA locus correlated with blood insulin levels (r = −0.228; 95% CI −0.424 – −0.019). D-loop low heteroplasmy correlated with fasting blood glucose (r = 0.275; 95% CI 0.062–0.464). Homoplasmies were associated with creatinine, blood urea nitrogen, and alkaline phosphatase. Intermediate heteroplasmy in mtDNA was associated with the monocyte cytokine secretion stimulation index (R2 = 0.156, P = 0.003). However, there was no significant association between mtDNA variability and the expression of the various genes.
Conclusions
Monocyte mtDNA shows relatively low variability. Low and Intermediate heteroplasmy are associated with cardiometabolic parameters, and intermediate heteroplasmy is associated with the monocyte cytokine secretion stimulation index.