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The C-1021T polymorphism of dopamine β-hydroxylase is not associated with orthostatic hypotension in a Chinese population

Journal of Human Hypertension volume 29, pages 173–178 (2015)Cite this article

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Abstract

To explore the association between the dopamine β-hydroxylase (DBH) gene C-1021T polymorphism and the occurrence of orthostatic hypotension (OH) in Chinese patients, the DBH C-1021T polymorphism was genotyped in 317 patients with OH and 664 age- and sex-matched controls with orthostatic normotension. All subjects underwent an upright posture study for the measurement of orthostatic blood pressure. OH was defined as a drop in blood pressure of 20/10 mm Hg or more within 3 min of assuming the upright posture. The allele frequency of the DBH C-1021T polymorphism in the orthostatic hypotensive group was similar to the orthostatic normotensive group (17.4 versus 14.9%, P>0.05). No statistical significant association was found between the distribution of the C-1021T genotypes and the risk of OH in both the orthostatic hypotensive and orthostatic normotensive groups even after adjustment for demographic parameters. Among the three different genotypes, blood pressure levels did not significantly differ in the general population in this study. The changes in orthostatic systolic or diastolic blood pressures among the different genotype groups were not detected (all P>0.05). The C-1021T polymorphism of the DBH was not associated with orthostatic hypotensive risk in a Chinese population.

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References

  1. Smith JJ, Porth CM, Erickson M . Hemodynamic response to the upright posture. J Clin Pharmacol 1994; 34 (5): 375–386.

    Article  CAS  Google Scholar 

  2. Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. The Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Neurology 1996; 46 (5): 1470.

  3. Masaki KH, Schatz IJ, Burchfiel CM, Sharp DS, Chiu D, Foley D et al. Orthostatic hypotension predicts mortality in elderly men: the Honolulu Heart Program. Circulation 1998; 98 (21): 2290–2295.

    Article  CAS  Google Scholar 

  4. Eigenbrodt ML, Rose KM, Couper DJ, Arnett DK, Smith R, Jones D . Orthostatic hypotension as a risk factor for stroke: the atherosclerosis risk in communities (ARIC) study, 1987-1996. Stroke 2000; 31 (10): 2307–2313.

    Article  CAS  Google Scholar 

  5. Rose KM, Tyroler HA, Nardo CJ, Arnett DK, Light KC, Rosamond W et al. Orthostatic hypotension and the incidence of coronary heart disease: the Atherosclerosis Risk in Communities study. Am J Hypertens 2000; 13 (6 Pt 1): 571–578.

    Article  CAS  Google Scholar 

  6. Lipsitz LA . Orthostatic hypotension in the elderly. New Engl J Med 1989; 321 (14): 952–957.

    Article  CAS  Google Scholar 

  7. Hajjar I . Postural blood pressure changes and orthostatic hypotension in the elderly patient: impact of antihypertensive medications. Drugs Aging 2005; 22 (1): 55–68.

    Article  CAS  Google Scholar 

  8. Gupta V, Lipsitz LA . Orthostatic hypotension in the elderly: diagnosis and treatment. Am J Med 2007; 120 (10): 841–847.

    Article  Google Scholar 

  9. Robertson D . The pathophysiology and diagnosis of orthostatic hypotension. Clin Auton Res 2008; 18 (Suppl 1): 2–7.

    Article  Google Scholar 

  10. Verwoert GC, Mattace-Raso FU, Hofman A, Heeringa J, Stricker BH, Breteler MM et al. Orthostatic hypotension and risk of cardiovascular disease in elderly people: the Rotterdam study. J Am Geriatr Soc 2008; 56 (10): 1816–1820.

    Article  Google Scholar 

  11. Benvenuto LJ, Krakoff LR . Morbidity and mortality of orthostatic hypotension: implications for management of cardiovascular disease. Am J Hypertens 2011; 24 (2): 135–144.

    Article  Google Scholar 

  12. Raiha I, Luutonen S, Piha J, Seppanen A, Toikka T, Sourander L . Prevalence, predisposing factors, and prognostic importance of postural hypotension. Arch Intern Med 1995; 155 (9): 930–935.

    Article  CAS  Google Scholar 

  13. Ooi WL, Barrett S, Hossain M, Kelley-Gagnon M, Lipsitz LA . Patterns of orthostatic blood pressure change and their clinical correlates in a frail, elderly population. JAMA 1997; 277 (16): 1299–1304.

    Article  CAS  Google Scholar 

  14. Cubells JF, Zabetian CP . Human genetics of plasma dopamine beta-hydroxylase activity: applications to research in psychiatry and neurology. Psychopharmacology (Berl) 2004; 174 (4): 463–476.

    Article  CAS  Google Scholar 

  15. Garland EM, Hahn MK, Ketch TP, Keller NR, Kim CH, Kim KS et al. Genetic basis of clinical catecholamine disorders. Ann NY Acad Sci 2002; 971: 506–514.

    Article  CAS  Google Scholar 

  16. Robertson D, Haile V, Perry SE, Robertson RM, Phillips JA 3rd, Biaggioni I . Dopamine beta-hydroxylase deficiency. A genetic disorder of cardiovascular regulation. Hypertension 1991; 18 (1): 1–8.

    Article  CAS  Google Scholar 

  17. Swoap SJ, Weinshenker D, Palmiter RD, Garber G . Dbh(−/−) mice are hypotensive, have altered circadian rhythms, and have abnormal responses to dieting and stress. Am J Physiol Regul Integr Comp Physiol 2004; 286 (1): R108–R113.

    Article  CAS  Google Scholar 

  18. Kobayashi K, Kurosawa Y, Fujita K, Nagatsu T . Human dopamine beta-hydroxylase gene: two mRNA types having different 3'-terminal regions are produced through alternative polyadenylation. Nucleic Acids Res 1989; 17 (3): 1089–2102.

    Article  CAS  Google Scholar 

  19. Zabetian CP, Anderson GM, Buxbaum SG, Elston RC, Ichinose H, Nagatsu T et al. A quantitative-trait analysis of human plasma-dopamine beta-hydroxylase activity: evidence for a major functional polymorphism at the DBH locus. Am J Hum Genet 2001; 68 (2): 515–522.

    Article  CAS  Google Scholar 

  20. Aoki K, Tazumi K, Takikawa K . Serum dopamine-beta-hydroxylase activity in essential hypertension and in chronic renal failure with hypertension. Jpn Circ J 1975; 39 (10): 1111–1114.

    Article  CAS  Google Scholar 

  21. Iseki F, Kuchii M, Nishio I, Masuyama Y . The evaluation of plasma dopamine beta-hydroxylase activity in essential and secondary hypertension. Jpn Heart J 1979; 20 (3): 307–320.

    Article  CAS  Google Scholar 

  22. Yeh TK, Yeh TC, Weng CF, Shih BF, Tsao HJ, Hsiao CH et al. Association of polymorphisms in genes involved in the dopaminergic pathway with blood pressure and uric acid levels in Chinese females. J Neural Transm 2010; 117 (12): 1371–1376.

    Article  CAS  Google Scholar 

  23. Fessel J, Robertson D . Orthostatic hypertension: when pressor reflexes overcompensate. Nat Clin Pract Nephrol 2006; 2 (8): 424–431.

    Article  Google Scholar 

  24. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr 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 (19): 2560–2572.

    Article  CAS  Google Scholar 

  25. Alberti KG, Zimmet PZ . Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998; 15 (7): 539–553.

    Article  CAS  Google Scholar 

  26. Perloff D, Grim C, Flack J, Frohlich ED, Hill M, McDonald M et al. Human blood pressure determination by sphygmomanometry. Circulation 1993; 88 (5 Pt 1): 2460–2470.

    Article  CAS  Google Scholar 

  27. Chen Y, Wen G, Rao F, Zhang K, Wang L, Rodriguez-Flores JL et al. Human dopamine beta-hydroxylase (DBH) regulatory polymorphism that influences enzymatic activity, autonomic function, and blood pressure. J Hypertens 2010; 28 (1): 76–86.

    Article  CAS  Google Scholar 

  28. Cubells JF, van Kammen DP, Kelley ME, Anderson GM, O'Connor DT, Price LH et al. Dopamine beta-hydroxylase: two polymorphisms in linkage disequilibrium at the structural gene DBH associate with biochemical phenotypic variation. Hum Genet 1998; 102 (5): 533–540.

    Article  CAS  Google Scholar 

  29. Oxenstierna G, Edman G, Iselius L, Oreland L, Ross SB, Sedvall G . Concentrations of monoamine metabolites in the cerebrospinal fluid of twins and unrelated individuals—a genetic study. J Psychiatr Res 1986; 20 (1): 19–29.

    Article  CAS  Google Scholar 

  30. Zabetian CP, Buxbaum SG, Elston RC, Kohnke MD, Anderson GM, Gelernter J et al. The structure of linkage disequilibrium at the DBH locus strongly influences the magnitude of association between diallelic markers and plasma dopamine beta-hydroxylase activity. Am J Hum Genet 2003; 72 (6): 1389–1400.

    Article  CAS  Google Scholar 

  31. Tang YL, Epstein MP, Anderson GM, Zabetian CP, Cubells JF . Genotypic and haplotypic associations of the DBH gene with plasma dopamine beta-hydroxylase activity in African Americans. Eur J Hum Genet 2007; 15 (8): 878–883.

    Article  CAS  Google Scholar 

  32. Tang Y, Anderson GM, Zabetian CP, Kohnke MD, Cubells JF . Haplotype-controlled analysis of the association of a non-synonymous single nucleotide polymorphism at DBH (+ 1603C —> T) with plasma dopamine beta-hydroxylase activity. Am J Med Genet B Neuropsychiatr Genet 2005; 139B (1): 88–90.

    Article  CAS  Google Scholar 

  33. Kohnke MD, Zabetian CP, Anderson GM, Kolb W, Gaertner I, Buchkremer G et al. A genotype-controlled analysis of plasma dopamine beta-hydroxylase in healthy and alcoholic subjects: evidence for alcohol-related differences in noradrenergic function. Biol Psychiatry 2002; 52 (12): 1151–1158.

    Article  CAS  Google Scholar 

  34. Bhaduri N, Mukhopadhyay K . Correlation of plasma dopamine beta-hydroxylase activity with polymorphisms in DBH gene: a study on Eastern Indian population. Cell Mol Neurobiol 2008; 28 (3): 343–350.

    Article  CAS  Google Scholar 

  35. Weinshilboum RM, Schorott HG, Raymond FA, Weidman WH, Elveback LR . Inheritance of very low serum dopamine-beta-hydroxylase activity. Am J Hum Genet 1975; 27 (5): 573–585.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Deinum J, Steenbergen-Spanjers GC, Jansen M, Boomsma F, Lenders JW, van Ittersum FJ et al. DBH gene variants that cause low plasma dopamine beta hydroxylase with or without a severe orthostatic syndrome. J Med Genet 2004; 41 (4): e38.

    Article  CAS  Google Scholar 

  37. DeStefano AL, Baldwin CT, Burzstyn M, Gavras I, Handy DE, Joost O et al. Autosomal dominant orthostatic hypotensive disorder maps to chromosome 18q. Am J Hum Genet 1998; 63 (5): 1425–1430.

    Article  CAS  Google Scholar 

  38. Pankow JS, Rose KM, Oberman A, Hunt SC, Atwood LD, Djousse L et al. Possible locus on chromosome 18q influencing postural systolic blood pressure changes. Hypertension 2000; 36 (4): 471–476.

    Article  CAS  Google Scholar 

  39. Harrap SB, Cui JS, Wong ZY, Hopper JL . Familial and genomic analyses of postural changes in systolic and diastolic blood pressure. Hypertension 2004; 43 (3): 586–591.

    Article  CAS  Google Scholar 

  40. Scurrah KJ, Zaloumis SG, Hopper JL, Harrap SB . Contribution of genes and environment to variation in postural changes in mean arterial and pulse pressure. J Hypertens 2008; 26 (12): 2319–2325.

    Article  CAS  Google Scholar 

  41. Schwartz F, Baldwin CT, Baima J, Gavras H . Mitochondrial DNA mutations in patients with orthostatic hypotension. Am J Med Genet 1999; 86 (2): 145–150.

    Article  CAS  Google Scholar 

  42. Winker R, Barth A, Valic E, Maier R, Osterode W, Pilger A et al. Functional adrenergic receptor polymorphisms and idiopathic orthostatic intolerance. Int Arch Occup Environ Health 2005; 78 (3): 171–177.

    Article  CAS  Google Scholar 

  43. Chen H, Ross CA, Wang N, Huo Y, MacKinnon DF, Potash JB et al. NEDD4L on human chromosome 18q21 has multiple forms of transcripts and is a homologue of the mouse Nedd4-2 gene. Eur J Hum Genet 2001; 9 (12): 922–930.

    Article  CAS  Google Scholar 

  44. Luo F, Wang Y, Wang X, Sun K, Zhou X, Hui R . A functional variant of NEDD4L is associated with hypertension, antihypertensive response, and orthostatic hypotension. Hypertension 2009; 54 (4): 796–801.

    Article  CAS  Google Scholar 

  45. Tabara Y, Kohara K, Miki T . Polymorphisms of genes encoding components of the sympathetic nervous system but not the renin-angiotensin system as risk factors for orthostatic hypotension. J Hypertens 2002; 20 (4): 651–656.

    Article  CAS  Google Scholar 

  46. North KE, Rose KM, Borecki IB, Oberman A, Hunt SC, Miller MB et al. Evidence for a gene on chromosome 13 influencing postural systolic blood pressure change and body mass index. Hypertension 2004; 43 (4): 780–784.

    Article  CAS  Google Scholar 

  47. Newton-Cheh C, Johnson T, Gateva V, Tobin MD, Bochud M, Coin L et al. Genome-wide association study identifies eight loci associated with blood pressure. Nat Genet 2009; 41 (6): 666–676.

    Article  CAS  Google Scholar 

  48. Levy D, Ehret GB, Rice K, Verwoert GC, Launer LJ, Dehghan A et al. Genome-wide association study of blood pressure and hypertension. Nat Genet 2009; 41 (6): 677–687.

    Article  CAS  Google Scholar 

  49. Gray IC, Campbell DA, Spurr NK . Single nucleotide polymorphisms as tools in human genetics. Hum Mol Genet 2000; 9 (16): 2403–2408.

    Article  CAS  Google Scholar 

  50. Risch N, Merikangas K . The future of genetic studies of complex human diseases. Science 1996; 273 (5281): 1516–1517.

    Article  CAS  Google Scholar 

  51. Lander ES, Schork NJ . Genetic dissection of complex traits. Science 1994; 265 (5181): 2037–2048.

    Article  CAS  Google Scholar 

  52. Mader SL, Josephson KR, Rubenstein LZ . Low prevalence of postural hypotension among community-dwelling elderly. JAMA 1987; 258 (11): 1511–1514.

    Article  CAS  Google Scholar 

  53. Wollner L, McCarthy ST, Soper ND, Macy DJ . Failure of cerebral autoregulation as a cause of brain dysfunction in the elderly. Br Med J 1979; 1 (6171): 1117–1118.

    Article  CAS  Google Scholar 

  54. Shin C, Abbott RD, Lee H, Kim J, Kimm K . Prevalence and correlates of orthostatic hypotension in middle-aged men and women in Korea: the Korean Health and Genome Study. J Hum Hypertens 2004; 18 (10): 717–723.

    Article  CAS  Google Scholar 

  55. Lipsitz LA, Storch HA, Minaker KL, Rowe JW . Intra-individual variability in postural blood pressure in the elderly. Clin Sci (Lond) 1985; 69 (3): 337–341.

    Article  CAS  Google Scholar 

  56. Tilvis RS, Hakala SM, Valvanne J, Erkinjuntti T . Postural hypotension and dizziness in a general aged population: a four-year follow-up of the Helsinki Aging Study. J Am Geriatr Soc 1996; 44 (7): 809–814.

    Article  CAS  Google Scholar 

  57. Mader SL . Aging and postural hypotension. An update. J Am Geriatr Soc 1989; 37 (2): 129–137.

    Article  CAS  Google Scholar 

  58. Tabara Y, Tachibana-Iimori R, Yamamoto M, Abe M, Kondo I, Miki T et al. Hypotension associated with prone body position: a possible overlooked postural hypotension. Hypertens Res 2005; 28 (9): 741–746.

    Article  Google Scholar 

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Acknowledgements

The study was supported by the Jilin Provincial Science Technology Department (No. 20070729–19 to Yang Zheng) and International S&T Cooperation Program of China (ISTCP; No. 2009DFB30050 to Hui Rutai).

Author Contributions

Na Lu, Rutai Hui, Yang Zheng designed the concept. Na Lu, Ye Yuan collected data. Na Lu, Jingzhou Chen, Ye Yuan, Xiaoqiang Cong, Yang Yang, Lin Meng, Kai Sun, Rutai Hui and Yang Zheng approved the article. Na Lu, Kai Sun and Yang Yang performed the statistical analyses.

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  1. N Lu and J Chen: First co-authors.

Authors and Affiliations

  1. The Pediatric Cardiology, The First Hospital of Jilin University, Changchun, China

    N Lu

  2. Hypertension Division, The Sino-German Laboratory of Molecular Medicine, Cardiovascular Institute and FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    J Chen, K Sun & R Hui

  3. The Anesthesiology Department, The First Hospital of Jilin University, Changchun, China

    Y Yuan

  4. The Cardiovascular Center, The First Hospital of Jilin University, Changchun, China

    X Cong, Y Yang, L Meng & Y Zheng

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Lu, N., Chen, J., Yuan, Y. et al. The C-1021T polymorphism of dopamine β-hydroxylase is not associated with orthostatic hypotension in a Chinese population. J Hum Hypertens 29, 173–178 (2015). https://doi.org/10.1038/jhh.2014.54

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