Carotid atherosclerosis-related mutations of mitochondrial DNA do not explain the phenotype of metabolic syndrome

Abstract

Aim: This study was undertaken to explore the relationship between metabolic syndrome (MetS) and atherosclerosis-related mitochondrial DNA (mtDNA) mutations, since MetS shares conventional and genetic risk factors with atherosclerosis.

Methods: The study involved 220 participants; the carotid ultrasonography followed by intima-media thickness (cIMT) measurement was used for quantitative diagnostics of carotid atherosclerosis. The diagnosis of MetS was set according to International Diabetes Federation criteria (IDF-2009). The level of mtDNA heteroplasmy in leukocytes was determined by qPCR. The severity of MetS was estimated on combination of serum HDL cholesterol, triglycerides and fasting glucose, systolic and diastolic blood pressure, and waist circumference measurements.

Results: MetS was present in 44 study participants. Ten mtDNA mutations were tested, and m.3336T>C and m.652delG heteroplasmy levels correlated with the clusterization of MetS symptoms, in particular the cardiovascular and metabolic risk factors, of triglyceride and fasting glucose levels. The other mtDNA mutations each only correlated with one symptom (i.e., m.652delG and m.12315G>A-with triglycerides; m.3256C>T, m.1555A>G, and m.15059G>A-with systolic blood pressure; m.14846G>A-with fasting glucose). There was no correlation between integral severity of MetS and cIMT.

Conclusion: In this study, the MetS phenotype was not explained directly by atherosclerosis-related mtDNA variants. It is possible to hypothesize that mtDNA-related mechanisms in atherosclerosis and MetS may be different, in spite of the similarity of several phenotypic characteristics.

Keywords

Metabolic syndrome / carotid atherosclerosis / mitochondrial DNA mutations / risk factors

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