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.
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.
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 (R 2 = 0.156, P = 0.003). However, there was no significant association between mtDNA variability and the expression of the various genes.
Monocyte mtDNA shows relatively low variability. In the study groups, several frequently occurring (5% to 20% within the group) heteroplasmic points are present: low heteroplasmic mtSNV m.310T>C and intermediate heteroplasmic mtSNVs m.16189T>C and m.15204T>C, while some alternative homoplasmies are much more common. Heteroplasmic mutations in mtDNA are associated with cardiometabolic parameters, including the degree of vascular stenosis and lipid and carbohydrate metabolism parameters, whereas alternative homoplasmies are associated with levels of alkaline phosphatase and both total and indirect bilirubin. Despite the low level of mtDNA variability, intermediate heteroplasmic mutations throughout mtDNA are associated with the monocyte cytokine secretion stimulation index.
https://www.xiahepublishing.com/1555-3884/GE-2025-00088
The study was recently published in the Gene Expression .
Gene Expression (GE) is an open-access journal. It was launched in 1991 by Chicago Medical School Press, and transferred to Cognizant Communication Corporation in 1994. From August 2022, GE is published by Xia & He Publishing Inc.
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Gene Expression
Associations of Mitochondrial Heteroplasmy in Blood Monocytes with Its Phenotypic Indices and Cardiometabolic Parameters in Metabolic Syndrome