Mitochondrial DNA Mutations In Maternally Inherited Essential Hypertensive Individuals

Objectives:The objective of the present study was to explore the mitochondrial DNA(mtDNA) variations in patients with essential hypertension(EHT), evaluate their roles in the pathogenesis and mechanism of hypertension.Methods:Samples used in this study were extracted from1000cases of EHT, who met the diagnostic standard of hypertension in WHO, and1000cases of normotensives (NT). Furthermore,92individuals from10maternally inherited essential hypertension pedigrees were collected in this study. All participants were evaluated and underwent a thorough examination, including medical record review, clinical evaluation, echocardiographic scanning, biochemical assay as well as genetic analysis. Genomic DNA was isolated from whole blood cells of participants. The hottest spots of hypertension were screened using oligodeoxynucleotides3777-4679and7908-8816, purified and subsequently analyzed by direct sequencing according to the revised consensus Cambridge sequence. The frequency, density, type and evolution conservative of mtDNA variations were comprehensively analyzed.Results:The results showed:1. The value of waist circumference, abdominal perimeter, BMI, triglyceride, low density lipoprotein cholesterol, blood glucose, creatinine, urea nitrogen and uric acid were significantly higher in EHT patients than those in NT (P<0.05).2. EHT patients had more mtDNA variations in frequency and density than NT. The mtDNA variations in regions of ND1, ND2, ATP6binding site were much more in EHT than NT(P<0.05).3. Among EHT patients, the mutation cases developed essential hypertension at earlier ages than the cases who did not carry the mutation (P<0.05); the average levels of left ventricular internal dimension in diastole(LVIDd) and left ventricular internal dimension in systole stroke volume(LVIDs) were higher in the mutation cases than the cases who did not carry the mutation, while the average levels of left ventricular ejection fraction(LVEF) were lower than the latter one.4. It was found that some maternally inherited EHT patients gathered in one family branch with pretty higher mutation frequency and density than those in other EHT patients and NT. Among the maternally inherited essential hypertensive individuals, there was microsatellite instability in mtDNA ND1C3970T, G3915A, tRNAIleA4295G, A4263G, tRNAMetC4457A, ND2A4658C, COXII G8152A, ATP8C8414T, A8459G, T8483C, ATP6C8684T and A8689C mutations.Conclusions:The results of this study demonstrated that the frequency and density of mtDNA variations were significantly higher in EHT than those in NT. Maternal transmission of hypertension has been implicated in some pedigrees, suggesting that the mutations in mtDNA is one of the molecular bases for this disorder. Our present results indicated that the mtDNA mutations might be involved in the pathogenesis of hypertension through altering the structure and function of the corresponding mitochondrion, mediating the over production of reactive oxidative species and disturbing cardiac structure and function with environmental factors, then resulting in the vascular endothelial dysfunction.