Mitochondrial DNA variability, particularly heteroplasmy, is associated with cardiometabolic parameters in patients with metabolic syndrome, according to a study released on July 14.
The cross-sectional study included 87 adult participants divided into three groups: 34 healthy blood donors as the control group, 21 obese patients, and 32 patients diagnosed with metabolic syndrome. Researchers performed blood biochemistry tests and isolated monocytes (CD14+ cells) from venous blood samples. Monocyte mitochondrial DNA was analyzed using next-generation sequencing to identify levels of heteroplasmy and homoplasmy. The expression of genes related to mitochondrial function was measured by quantitative real-time polymerase chain reaction. Additionally, monocytes were cultured both with and without lipopolysaccharide for 24 hours to assess cytokine secretion stimulation.
The findings showed that monocyte mitochondrial DNA had low overall variability but significantly more frequent alternative homoplasmies. Intermediate and low heteroplasmy from protein-coding regions correlated positively with vascular stenosis (r = 0.396; 95% CI 0.067–0.647) and negatively with low-density lipoprotein levels (r = −0.258; 95% CI −0.45 – −0.043). Intermediate heteroplasmy from rRNA regions correlated negatively with blood insulin levels (r = −0.228; 95% CI −0.424 – −0.019), while D-loop low heteroplasmy correlated positively 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 heteroplasmic mutations throughout the mitochondrial genome were found to be associated with the monocyte cytokine secretion stimulation index (R2 = 0.156, P = 0.003). However, no significant association was observed between mitochondrial DNA variability and gene expression related to mitochondrial biogenesis or oxidative stress systems.
The study identified several frequently occurring heteroplasmic points within each group: low heteroplasmic mtSNV m.310T>C and intermediate heteroplasmic mtSNVs m.16189T>C and m.15204T>C were noted as common variants among participants, while some alternative homoplasmies appeared more often than others.
