Mitochondrial DNA 7908–8816 region mutations in maternally inherited essential hypertensive subjects in China

Abstract

BackgroundNuclear genes or family-based mitochondrial screening have been the focus of genetic studies into essential hypertension. Studies into the role of mitochondria in sporadic Chinese hypertensives are lacking. The objective of the study was to explore the relationship between mitochondrial DNA (mtDNA) variations and the development of maternally inherited essential hypertension (MIEH) in China.MethodsYangzhou residents who were outpatients or in-patients at the Department of Cardiology in Northern Jiangsu People’s Hospital (Jiangsu, China) from June 2009 to June 2015 were recruited in a 1:1 case control study of 600 gender-matched Chinese MIEH subjects and controls. Genomic DNA was isolated from whole blood cells. The most likely sites for hypertension were screened using oligodeoxynucleotides at positions 7908–8816, purified and subsequently analyzed by direct sequencing according to the revised consensus Cambridge sequence. The frequency, density, type and conservative evolution of mtDNA variations were comprehensively analyzed.ResultsWe found a statistical difference between the two groups for body mass index, waist circumference, abdominal circumference, triglyceride, low-density lipoprotein cholesterol, fasting blood glucose, uric acid, creatinine and blood urea nitrogen (P < 0.05). More amino-acid changes and RNA variants were found in MIEH subjects than the controls (P < 0.01). The detection system simultaneously identified 40 different heteroplasmic or homoplasmic mutations in 4 genes: COXII, tRNALys, ATP8 and ATP 6. The mtDNA variations were mainly distributed in regions of ATP6 binding sites, and the site of highest mutation frequency was m. 8414C > T. Three changes in single bases (C8414T in ATP8, A8701G in ATP6 and G8584A in ATP6) were significantly different in the MIEH patients and the controls (P < 0.001). The m.8273_8281del mutation was identified from 59 MIEH patients.ConclusionsOur results indicate that novel mtDNA mutations may be involved in the pathological process of MIEH, and mitochondrial genetic characteristics were identified in MIEH individuals.Electronic supplementary materialThe online version of this article (10.1186/s12920-018-0408-0) contains supplementary material, which is available to authorized users.

Identification of novel mitochondrial and mitochondrial related genetic loci associated with exercise response in the Gene SMART study

“…A cumulative total of 4,325 NEMP variants and 28 mitochondrial variants passed the nominal threshold of significance (P unadjusted <0.05) for all tests. A solar plot showing the clustering of mitochondrial genomic variants for each trait is shown in Fig 1 (23)(23)(33). The exonic variants passing the nominal threshold from the mitochondrial association results are summarised in Table 3 .…”

“…The g.A8701G variant within the ATP6 gene causes a missense change within its respective protein (p.Thr59Ala) and has been well characterised in hypertensive cases (33). This variant was nominally significant in both the Δ-LT phenotype and the PC3 composite trait within the cohort.…”

The mitochondrial tRNAAla 5587T>C and tRNALeu(CUN) 12280A>G mutations may be associated with hypertension in a Chinese family

“…Although many studies revealed the genetics of mitochondrial disorders, the molecular mechanism underlying hypertension remains unclear (22,23). Experimental studies identified a positive association between mtDNA mutations and hypertension (24,25). In particular, Watson et al (26) reported a double ND3 10398A>G Ddel CO1 HaeIII 6620T>C or 6260G>A mutation in hypertensive African-Americans with end-stage renal disease.…”

Associations of Mitochondrial DNA 3777-4679 region mutations with maternally inherited essential hypertensive subjects in China.

“…PCR cycle program was carried out in a 9700 Thermocycler (Perkin-Elmer Applied Biosystems, Norwalk, USA). Each fragment had been purified and sequenced by ABI 3730 Sequence Analysis software (Applied Biosystems, Inc., Foster City, CA, USA) using the BigDye Terminator v1.1 kit (ABI Company, Carlsbad, CA, USA), and subsequently SeqWeb program GAP(GCG) was analyzed and compared with the updated consensus Cambridge Sequence [17,18]. Pathogenic variants were identified from the mitochondrial map (http://www.mitomap.org/) [19].…”