Background and purpose
Mitochondrial DNA (mtDNA) diversity, particularly heteroplasmy, is thought to influence cellular immune biogenesis, particularly in monocytes of metabolic syndrome (MetS). This study aimed to determine the association between monocyte mtDNA variability and phenotypic indicators such as cytokine secretion and gene expression, as well as cardiometabolic parameters, in MetS patients.
method
This cross-sectional study recruited 87 adult participants, including 34 healthy blood donors (control group), 21 obese patients (obese group), and 32 patients with MetS (MetS group). Blood chemistry 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 moderate (10–95%) heteroplasmy, as well as homoplasmy (≥95%). The expression of genes related to mitochondrial biogenesis, mitochondrial uncoupling, oxidative stress systems, and NF-κB signaling was assessed by quantitative real-time polymerase chain reaction. Monocytes cultured for 24 h in the presence and absence of lipopolysaccharide were analyzed by enzyme-linked immunosorbent assay to assess the cytokine secretion stimulation index.
result
Although monocyte mtDNA showed low variability, alternative homoplasmy was significantly common. Intermediate and low heteroplasmy from protein-coding loci correlated with stenosis (r = 0.396; 95% confidence interval (CI) 0.067 to 0.647) and low-density lipoprotein levels (r = −0.258; 95% CI −0.45 to −0.043). Intermediate heteroplasmy from rRNA loci correlated with blood insulin levels (r = −0.228; 95% CI −0.424 – −0.019). Low heteroplasmy in the D-loop correlated with fasting blood glucose (r = 0.275; 95% CI 0.062 to 0.464). Homoplasmy was associated with creatinine, blood urea nitrogen, and alkaline phosphatase. Intermediate heteroplasmy of mtDNA was associated with monocyte cytokine secretion stimulation index (R2 = 0.156, P = 0.003). However, there was no significant association between mtDNA variability and the expression of various genes.
conclusion
Monocyte mtDNA exhibits relatively low variability. In the study group, there are several frequently occurring (5% to 20% within group) heteroplasmy points. Low heteroplasmic mtSNV m.310T>C and intermediate heteroplasmic mtSNV m.16189T>C and m.15204T>C, but some alternative homoplasmies are more common. Heteroplasmy mutations in mtDNA are associated with cardiometabolic parameters such as the degree of vascular stenosis and lipid and carbohydrate metabolic parameters, whereas alternative homoplasmy mutations are associated with levels of alkaline phosphatase and both total and indirect bilirubin. Despite low mtDNA variability, intermediate heteroplasmic mutations throughout mtDNA are associated with monocyte cytokine secretion stimulation index.
sauce:
Reference magazines:
Voronova, S. others. (2026). Mitochondrial heteroplasmy in blood monocytes and its association with phenotypic indicators and cardiometabolic parameters in metabolic syndrome: a pilot cross-sectional study. gene expression. DOI: 10.14218/ge.2025.00088. https://www.xiahepublishing.com/1555-3884/GE-2025-00088
