Abstract
Earlier genetic studies of essential hypertension have focused on nuclear genes or family-based mitochondrial screening in Caucasian and African-American pedigrees. The role of mitochondria in sporadic Chinese hypertensives is unknown. We sequenced mitochondrial genomes in 306 age- and gender-balanced Chinese Han hypertensives and controls. In 153 hypertensives, putative functional changes included 4 changes in rRNA genes, 11 changes in tRNA genes and 25 amino-acid substitutions. The remaining variants were synonymous changes or non-coding regions. In the 153 controls, 2 base changes in the tRNA genes and 13 amino-acid substitutions were found. A8701G in ATP6 gene (belongs to haplogroup M; P=0.0001) and C8414T in ATP8 gene (belongs to haplogroup D; P=0.01) were detected significantly different in the cases and controls. Interestingly, the cases were more likely to have two or more amino-acid changes and RNA variants compared with the controls (57.43 versus 23.81%, P=0.0001). In addition, several variants we found were highly conserved and/or specifically located at the 3′ end adjacent to the anticodon, which may contribute to the stabilization of structure, and thus lead to the decrease of tRNA metabolism. In conclusion, mitochondrial SNPs (mtSNPs) may affect the course of hypertension in sporadic Chinese hypertensives. Some specific mtSNP within mitochondria may have potential role in the Chinese hypertensives due to their function. Synergetic interaction between mitochondrial mtSNPs and/or haplogroups is needed to be investigated in the future.
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References
Chobanian AV, Bakris GL, Black HR et al: The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA 2003; 289: 2560–2572.
Liu LS : 2005 Guidelines for prevention and treatment of hypertension in China. Beijing: People's medical publishing house, 2007, pp 1–8.
Harrap SB : Where are all the blood-pressure genes? Lancet 2003; 361: 2149–2151.
Bonnardeaux A, Davies E, Jeunemaitre X et al: Angiotensin II type 1 receptor gene polymorphisms in human essential hypertension. Hypertension 1994; 24: 63–69.
Caulfield M, Munroe P, Pembroke J et al: Genome-wide mapping of human loci for essential hypertension. Lancet 2003; 361: 2118–2123.
Kamide K, Kokubo Y, Fukuhara S et al: Protein tyrosine kinase 2beta as a candidate gene for hypertension. Pharmacogenet Genomics 2007; 17: 931–939.
Banno M, Hanada H, Kamide K et al: Association of genetic polymorphisms of endothelin-converting enzyme-1 gene with hypertension in a Japanese population and rare missense mutation in preproendothelin-1 in Japanese hypertensives. Hypertens Res 2007; 30: 513–520.
Kulah E, Dursun A, Aktunc E et al: Effects of angiotensin-converting enzyme gene polymorphism and serum vitamin D levels on ambulatory blood pressure measurement and left ventricular mass in Turkish hypertensive population. Blood Press Monit 2007; 12: 207–213.
Wallace DC : Mitochondrial diseases in man and mouse. Science 1999; 283: 1482–1488.
Hirano M, Davidson M, DiMauro S : Mitochondria and the heart. Curr Opin Cardiol 2001; 16: 201–210.
Lassègue B, Griendling KK : Reactive oxygen species in hypertension; an update. Am J Hypertens 2004; 17: 852–860.
Hutchinson J, Crawford MH : Genetic determinants of blood pressure level among the Black Caribs of St Vincent. Hum Biol 1981; 53: 453–466.
DeStefano AL, Gavras H, Heard-Costa N et al: Maternal component in the familial aggregation of hypertension. Clin Genet 2001; 60: 13–21.
Yang Q, Kim SK, Sun F et al: Maternal influence on blood pressure suggests involvement of mitochondrial DNA in the pathogenesis of hypertension: the Framingham Heart Study. J Hypertens 2007; 25: 2067–2073.
Wilson FH, Hariri A, Farhi A et al: A cluster of metabolic defects caused by mutation in a mitochondrial tRNA. Science 2004; 306: 1190–1194.
Zhu H, Wang S : Mitochondria and left ventricular hypertrophy. J Geriatr Cardiol 2008; 5: 50–59.
Anderson S, Bankier AT, Barrell BG et al: Sequence and organization of the human mitochondrial genome. Nature 1981; 290: 457–465.
Ingman M, Gyllensten U : mtDB: Human mitochondrial genome database, a resource for population genetics and medical sciences. Nucleic Acids Res 2005; 34: 749–751.
Ruiz-Pesini E, Lott MT, Procaccio V et al: An enhanced MITOMAP with a global mtDNA mutational phylogeny. Nucleic Acids Res 2007; 35: 823–828.
Herrnstadt C, Elson JL, Fahy E et al: Reduced–median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups. Am J Hum Genet 2002; 70: 1152–1171.
Nishigaki Y, Yamada Y, Fuku N et al: Mitochondrial haplogroup N9b is protective against myocardial infarction in Japanese males. Hum Genet 2007; 120: 827–836.
Wallace DC : Mitochondrial DNA sequence variation in human evolution and disease. Proc Natl Acad Sci USA 1994; 91: 8739–8746.
Nishigaki Y, Yamada Y, Fuku N et al: Mitochondrial haplogroup A is a genetic risk factor for atherothrombotic cerebral infarction in Japanese females. Mitochondrion 2007; 7: 72–79.
Guo LJ, Oshida Y, Fuku N et al: Mitochondrial genome polymorphisms associated with type-2 diabetes or obesity. Mitochondrion 2005; 5: 15–33.
Dato S, Passarino G, Rose G et al: Association of the mitochondrial DNA haplogroup J with longevity is population specific. Eur J Hum Genet 2004; 12: 1080–1082.
Kazuno AA, Munakata K, Nagai T et al: Identification of mitochondrial DNA polymorphisms that alter mitochondrial matrix pH and intracellular calcium dynamics. PLoS Genet 2006; 2: e128.
Rice T, Rankinen T, Province MA et al: Genome-wide linkage analysis of systolic and diastolic blood pressure: the Quebec Family Study. Circulation 2000; 102: 1956–1963.
Yang Z, Venardos K, Jones E et al: Identification of a novel polymorphism in the 3′UTR of the L-arginine transporter gene SLC7A1: contribution to hypertension and endothelial dysfunction. Circulation 2007; 115: 1269–1274.
Amamoto K, Okamura T, Tamaki S et al: Epidemiologic study of the association of low-Km mitochondrial acetaldehyde dehydrogenase genotypes with blood pressure level and the prevalence of hypertension in a general population. Hypertens Res 2002; 25: 857–864.
Lodi R, Montagna P, Cortelli P et al: ‘Secondary’ 4216/ND1 and 13708/ND5 Leber's hereditary optic neuropathy mitochondrial DNA mutations do not further impair in vivo mitochondrial oxidative metabolism when associated with the 11778/ND4 mitochondrial DNA mutation. Brain 2000; 123: 1896–1902.
Xu L, Hu Y, Chen B et al: Mitochondrial polymorphisms as risk factors for endometrial cancer in southwest China. Int J Gynecol Cancer 2006; 16: 1661–1667.
Acknowledgements
We thank all the participants of investigation, sophisticated clinical data collection of Chunlin Zeng, experienced data analyzing of Xinyuan Tong.This study was supported by grants from Chinese National Natural Science Funds (Capital Developmental Grant—key project no.:2003-2019) and National Institutes of Health HL69712 (DWB).
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Zhu, HY., Wang, SW., Martin, L. et al. The role of mitochondrial genome in essential hypertension in a Chinese Han population. Eur J Hum Genet 17, 1501–1506 (2009). https://doi.org/10.1038/ejhg.2009.63
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DOI: https://doi.org/10.1038/ejhg.2009.63
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