A Novel 5’-Uncoding Region -1248 A>G Variation of Mitofusin-2 Gene Is Associated with Hypertension in Chinese
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose: Mitofusin2 gene (Mfn2, also named Hyperplasia suppressive gene, HSG) is very important in the origin and development of hypertension. However, the mechanism of Mfn2/HSG expression regulation was not uncovered. This study was designed to explore the association of a novel 5’-uncoding region (UCR) -1248 A>G variation of HSG/Mfn2 gene and hypertension. Materials and Methods: 472 healthy, normotensive subjects [normotension (NT) group], 454 prehypertensive subjects [prehypertension (PH) group] and 978 hypertensive patients [essential hypertension (EH) group] were screened for an association study between 5’-UCR -1248 A>G of Mfn2/HSG and hypertension by polymerase chain reaction and DNA sequencing after venous blood was drawn and DNA was extracted. Results: When comparing the A and G frequency in EH, PH and NT groups, in total, NT group significantly had higher A frequency than in PH group [odds ratio (OR)=1.605, confidence interval (CI) 95%=1.063-2.242, p=0.025] and EH group (OR=5.395, CI 95%=3.783-7.695, p<0.01). When subgrouped by gender, A frequency in NT group was still significantly higher than in EH group (male: OR= 4.264, CI 95%=2.780-6.543, p<0.01; female: OR=8.897, CI 95%=4.686-16.891, p<0.01), but not from PH group, either in male group or in female group. Ordinal Logistic Regression analysis showed that A>G variation was significantly related with blood pressure level (B=-1.271, Wald=40.914, CI 95%=-1.660 - -0.881, p<0.01). Conclusion: 5’-UCR -1248 A>G variation of Mfn2/HSG gene was a novel variation and may be associated with hypertension in Chinese.
Abstract
Purpose: Mitofusin2 gene (Mfn2, also named Hyperplasia suppressive gene, HSG) is very important in the origin and development of hypertension. However, the mechanism of Mfn2/HSG expression regulation was not uncovered. This study was designed to explore the association of a novel 5’-uncoding region (UCR) -1248 A>G variation of HSG/Mfn2 gene and hypertension. Materials and Methods: 472 healthy, normotensive subjects [normotension (NT) group], 454 prehypertensive subjects [prehypertension (PH) group] and 978 hypertensive patients [essential hypertension (EH) group] were screened for an association study between 5’-UCR -1248 A>G of Mfn2/HSG and hypertension by polymerase chain reaction and DNA sequencing after venous blood was drawn and DNA was extracted. Results: When comparing the A and G frequency in EH, PH and NT groups, in total, NT group significantly had higher A frequency than in PH group [odds ratio (OR)=1.605, confidence interval (CI) 95%=1.063-2.242, p=0.025] and EH group (OR=5.395, CI 95%=3.783-7.695, p<0.01). When subgrouped by gender, A frequency in NT group was still significantly higher than in EH group (male: OR= 4.264, CI 95%=2.780-6.543, p<0.01; female: OR=8.897, CI 95%=4.686-16.891, p<0.01), but not from PH group, either in male group or in female group. Ordinal Logistic Regression analysis showed that A>G variation was significantly related with blood pressure level (B=-1.271, Wald=40.914, CI 95%=-1.660 - -0.881, p<0.01). Conclusion: 5’-UCR -1248 A>G variation of Mfn2/HSG gene was a novel variation and may be associated with hypertension in Chinese.
참고문헌 (20)
- Huang P, "Control of mitochondrial morphology through differential interactions of mitochondrial fusion and fission proteins", PLoS One, 6, pp.e20655~ (2011)
- Liesa M, "Mitochondrial dynamics in mammalian health and disease", Physiol Rev, 89, pp.799~845 (2009)
- Chen KH, "Dysregulation of HSG triggers vascular proliferative disorders", Nat Cell Biol, 6, pp.872~883 (2004)
- Liu YP, "Hyperplasia suppressor gene expression in vascular smooth muscle cells derived from normotensive and hypertensive patients underwent bypass surgery", Zhonghua Xin Xue Guan Bing Za Zhi, 35, pp.914~918 (2007)
- de Brito OM, "Mitofusin-2 regulates mitochondrial and endoplasmic reticulum morphology and tethering: the role of Ras", Mitochondrion, 9, pp.222~226 (2009)
- Pashkow FJ, "Oxidative Stress and Inflammation in Heart Disease: Do Antioxidants Have a Role in Treatment and", or Prevention?, 2011, pp.2011, 514623~
- Guo X, "Mitofusin 2 triggers vascular smooth muscle cell apoptosis via mitochondrial death pathway", Circ Res, 101, pp.1113~1122 (2007)
- Yu H, "Mitofusin 2 inhibits angiotensin II-induced myocardial hypertrophy", J Cardiovasc Pharmacol Ther, 16, pp.205~211 (2011)
- Wang Z, "HSG", Mfn2 gene polymorphism and essential hypertension: a case-control association study in Chinese, 2011, pp.18, 24~31
- Farré D, "Identification of patterns in biological sequences at the ALGGEN server: PROMO and MALGEN", Nucleic Acids Res, 31, pp.3651~3653 (2003)
- Lenfant C, "Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Seventh report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7): resetting the hypertension sails", Hypertension, 41, pp.1178~1179 (2003)
- Wang Z, "Is prehypertension really different from normotension and hypertension? A case-control pilot proteomic study in Chinese", Clin Exp Hypertens, 31, pp.316~329 (2009)
- Wang Z, "E-selectin gene polymorphisms are associated with essential hypertension: a case-control pilot study in a Chinese population", BMC Med Genet, 11, pp.127~ (2010)
- Sato-Otsubo A, "Single-nucleotide polymorphism array karyotyping in clinical practice: where, when, and how?", Semin Oncol, 39, pp.13~25 (2012)
- O’Neill SM, "Transcriptional regulation of the human neutral ceramidase gene", Arch Biochem Biophys, 511, pp.21~30 (2011)
- Zhang K, "Common functional genetic variants in catecholamine storage vesicle protein promoter motifs interact to trigger systemic hypertension", J Am Coll Cardiol, 55, pp.1463~1475 (2010)
- Katkoori VR, "Clinical significance of a novel single nucleotide polymorphism in the 5’ untranslated region of the Rabphillin-3A-Like gene in colorectal adenocarcinoma", Front Biosci, 13, pp.1050~1061 (2008)
- Li N, "Genetic variation of NEDD4L is associated with essential hypertension in female Kazakh general population: a case-control study", BMC Med Genet, 10, pp.130~ (2009)
- Pimenta E, "Prehypertension: epidemiology, consequences and treatment", Nat Rev Nephrol, 6, pp.21~30 (2010)
- Selassie A, "Progression is accelerated from prehypertension to hypertension in blacks", Hypertension, 58, pp.579~587 (2011)