Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

Hypertension Research
  • View all journals
  • Search
  • Log in
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. hypertension research
  3. original article
  4. article
Interaction of Angiotensin I–Converting Enzyme Insertion-Deletion Polymorphism and Daily Salt Intake Influences Hypertension in Japanese Men
Download PDF
Download PDF
  • Original Article
  • Published: 01 October 2006

Interaction of Angiotensin I–Converting Enzyme Insertion-Deletion Polymorphism and Daily Salt Intake Influences Hypertension in Japanese Men

  • Ling Zhang1,
  • Koichi Miyaki1,2,
  • Jungo Araki1,
  • Yixuan Song1,
  • Tomomi Kimura1,
  • Kazuyuki Omae2 &
  • …
  • Masaaki Muramatsu1 

Hypertension Research volume 29, pages 751–758 (2006)Cite this article

  • 2308 Accesses

  • Metrics details

Abstract

The contribution of angiotensin I–converting enzyme insertion-deletion polymorphism (ACE I/D) to salt-sensitivity hypertension has been extensively studied by means of salt-loading tests, but whether or not the interaction with daily salt intake affects blood pressure still remains to be clarified. We therefore conducted a cross-sectional study of 284 Japanese male workers (age range, 20–64 years) to examine the effect of ACE I/D genotype and daily salt intake on hypertension. Blood pressure was measured and the ACE I/D was identified by polymerase chain reaction (PCR). Daily salt intake was calculated from a food frequency questionnaire (FFQ). In multivariate analyses, we explored the interaction of ACE I/D and salt intake by means of logistic regression analysis and multiple linear regression analysis. ACE I/D per se was not associated with blood pressure levels or hypertension. ACE I/D interacted with daily salt intake and correlated with hypertension (p for interaction=0.047). In the ID+II genotype, hypertension was increased by high salt intake (p=0.005), while in the DD genotype it was not (p=0.257). The interaction was more prominent in the overweight group (p=0.039) than in non-overweight group. In the overweight group, high salt intake induced a 10.5 mmHg higher diastolic blood pressure in the ID+II genotype than in the DD genotype (p=0.042). Our results suggest that ACE I/D and daily salt intake constitute a gene-environment interaction, which may be further modulated by overweight.

Similar content being viewed by others

Genetic variation in salt taste receptors impact salt intake and blood pressure

Article Open access 10 March 2023

Effects of polygenic risk score and sodium and potassium intake on hypertension in Asians: A nationwide prospective cohort study

Article Open access 10 July 2024

The association between salt intake and blood pressure is mediated by body mass index but modified by hypertension: The ELSA-Brasil study

Article 25 June 2022

Article PDF

References

  1. Muntzel M, Drueke T : A comprehensive review of the salt and blood pressure relationship. Am J Hypertens 1992; 5: 1S–42S.

    Article  CAS  PubMed  Google Scholar 

  2. Freis ED : The role of salt in hypertension. Blood Press 1992; 1: 196–200.

    Article  CAS  PubMed  Google Scholar 

  3. Weinberger MH : Salt sensitivity of blood pressure in humans. Hypertension 1996; 27: 481–490.

    Article  CAS  PubMed  Google Scholar 

  4. Weinberger MH : Salt sensitive human hypertension. Endocr Res 1991; 17: 43–51.

    Article  CAS  PubMed  Google Scholar 

  5. Luft FC, Weinberger MH : Heterogeneous responses to changes in dietary salt intake: the salt-sensitivity paradigm. Am J Clin Nutr 1997; 65: 612S–617S.

    Article  CAS  PubMed  Google Scholar 

  6. Luft FC, Miller JZ, Weinberger MH, Christian JC, Skrabal F : Genetic influences on the response to dietary salt reduction, acute salt loading, or salt depletion in humans. J Cardiovasc Pharmacol 1988; 12 ( Suppl 3): S49–S55.

    Article  PubMed  Google Scholar 

  7. Cowley AW Jr : Genetic and nongenetic determinants of salt sensitivity and blood pressure. Am J Clin Nutr 1997; 65: 587S–593S.

    Article  CAS  PubMed  Google Scholar 

  8. Tamaki S, Nakamura Y, Tabara Y, et al: Combined analysis of polymorphisms in angiotensinogen and adducin genes and their effects on hypertension in a Japanese sample: the Shigaraki Study. Hypertens Res 2005; 28: 645–650.

    Article  CAS  PubMed  Google Scholar 

  9. Yamagishi K, Iso H, Tanigawa T, Cui R, Kudo M, Shimamoto T : High sodium intake strengthens the association between angiotensinogen T174M polymorphism and blood pressure levels among lean men and women: a community-based study. Hypertens Res 2004; 27: 53–60.

    Article  CAS  PubMed  Google Scholar 

  10. Kikuya M, Sugimoto K, Katsuya T, et al: A/C1166 gene polymorphism of the angiotensin II type 1 receptor (AT1) and ambulatory blood pressure: the Ohasama Study. Hypertens Res 2003; 26: 141–145.

    Article  CAS  PubMed  Google Scholar 

  11. Jin JJ, Nakura J, Wu Z, et al: Association of angiotensin II type 2 receptor gene variant with hypertension. Hypertens Res 2003; 26: 547–552.

    Article  CAS  PubMed  Google Scholar 

  12. Ono K, Mannami T, Baba S, Yasui N, Ogihara T, Iwai N : Lack of association between angiotensin II type 1 receptor gene polymorphism and hypertension in Japanese. Hypertens Res 2003; 26: 131–134.

    Article  CAS  PubMed  Google Scholar 

  13. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F : An insertion/deletion polymorphism in the angiotensin I–converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990; 86: 1343–1346.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Higaki J, Baba S, Katsuya T, et al: Deletion allele of angiotensin-converting enzyme gene increases risk of essential hypertension in Japanese men: the Suita Study. Circulation 2000; 101: 2060–2065.

    Article  CAS  PubMed  Google Scholar 

  15. Henskens LH, Spiering W, Stoffers HE, et al: Effects of ACE I/D and A T1R–A1166C polymorphisms on blood pressure in a healthy normotensive primary care population: first results of the Hippocates study. J Hypertens 2003; 21: 81–86.

    Article  CAS  PubMed  Google Scholar 

  16. Wang JG, Liu L, Zagato L, et al: Blood pressure in relation to three candidate genes in a Chinese population. J Hypertens 2004; 22: 937–944.

    Article  CAS  PubMed  Google Scholar 

  17. Gesang L, Liu G, Cen W, et al: Angiotensin-converting enzyme gene polymorphism and its association with essential hypertension in a Tibetan population. Hypertens Res 2002; 25: 481–485.

    Article  CAS  PubMed  Google Scholar 

  18. Jeng JR : Carotid thickening, cardiac hypertrophy, and angiotensin converting enzyme gene polymorphism in patients with hypertension. Am J Hypertens 2000; 13: 111–119.

    Article  CAS  PubMed  Google Scholar 

  19. Tiret L, Blanc H, Ruidavets JB, et al: Gene polymorphisms of the renin-angiotensin system in relation to hypertension and parental history of myocardial infarction and stroke: the PEGASE study. Projet d'Etude des Genes de l'Hypertension Arterielle Severe a moderee Essentielle. J Hypertens 1998; 16: 37–44.

    Article  CAS  PubMed  Google Scholar 

  20. Cambien F, Poirier O, Lecerf L, et al: Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 1992; 359: 641–644.

    Article  CAS  PubMed  Google Scholar 

  21. Sekuri C, Cam FS, Ercan E, et al: Renin-angiotensin system gene polymorphisms and premature coronary heart disease. J Renin Angiotensin Aldosterone Syst 2005; 6: 38–42.

    Article  CAS  PubMed  Google Scholar 

  22. Saeed M, Saleheen D, Siddiqui S, Khan A, Butt ZA, Frossard PM : Association of angiotensin converting enzyme gene polymorphisms with left ventricular hypertrophy. Hypertens Res 2005; 28: 345–349.

    Article  CAS  PubMed  Google Scholar 

  23. Kuznetsova T, Staessen JA, Stolarz K, et al: Relationship between left ventricular mass and the ACE D/I polymorphism varies according to sodium intake. J Hypertens 2004; 22: 287–295.

    Article  CAS  PubMed  Google Scholar 

  24. Giner V, Poch E, Bragulat E, et al: Renin-angiotensin system genetic polymorphisms and salt sensitivity in essential hypertension. Hypertension 2000; 35: 512–517.

    Article  CAS  PubMed  Google Scholar 

  25. Poch E, Gonzalez D, Giner V, Bragulat E, Coca A, de La Sierra A : Molecular basis of salt sensitivity in human hypertension. Evaluation of renin-angiotensin-aldosterone system gene polymorphisms. Hypertension 2001; 38: 1204–1209.

    Article  CAS  PubMed  Google Scholar 

  26. Hiraga H, Oshima T, Watanabe M, et al: Angiotensin I–converting enzyme gene polymorphism and salt sensitivity in essential hypertension. Hypertension 1996; 27: 569–572.

    Article  CAS  PubMed  Google Scholar 

  27. Torheim LEBI, Hatloy A, Diakite M, et al: Validation of a quantitative food-frequency questionnaire for use in Western Mali. Public Health Nutr 2001; 4: 1267–1277.

    Article  CAS  PubMed  Google Scholar 

  28. Cooper R, McFarlane-Anderson N, Bennett FI, et al: ACE, angiotensinogen and obesity: a potential pathway leading to hypertension. J Hum Hypertens 1997; 11: 107–111.

    Article  CAS  PubMed  Google Scholar 

  29. Ruano M, Silvestre V, Castro R, et al: Morbid obesity, hypertensive disease and the renin-angiotensin-aldosterone axis. Obes Surg 2005; 15: 670–676.

    Article  CAS  PubMed  Google Scholar 

  30. Choo V : WHO reassesses appropriate body-mass index for Asian populations. Lancet 2002; 360: 235.

    Article  PubMed  Google Scholar 

  31. Sipe JC, Waalen J, Gerber A, Beutler E : Overweight and obesity associated with a missense polymorphism in fatty acid amide hydrolase (FAAH). Int J Obes Relat Metab Disord 2005; 29: 755–759.

    Article  CAS  Google Scholar 

  32. WHO/IASO/IOTF : The Asia-Pacific Perspective: Redefining Obesity and Its Treatment. Victoria, Health Communications Australia Pty Ltd, 2000.

  33. Takahashi K, Yoshimura Y, Kaimoto T, Kunii D, Komatsu T, Yamamoto S : Validation of a food frequency questionnaire based on food groups for estimating individual nutrient intake. Jpn J Nutr 2001; 59: 221–232 ( in Japanese).

    Article  Google Scholar 

  34. Willett W, Lenart E : Reproducibility and validity of food-frequency questionnaires, in Willett W ( ed): Nutritional Epidemiology, 2nd ed. New York, Oxford University Press, 1998, pp 101–147.

    Chapter  Google Scholar 

  35. Lindpaintner K, Pfeffer MA, Kreutz R, et al: A prospective evaluation of an angiotensin-converting–enzyme gene polymorphism and the risk of ischemic heart disease. N Engl J Med 1995; 332: 706–711.

    Article  CAS  PubMed  Google Scholar 

  36. Kato N, Sugiyama T, Morita H, et al: Comprehensive analysis of the renin-angiotensin gene polymorphisms with relation to hypertension in the Japanese. J Hypertens 2000; 18: 1025–1032.

    Article  CAS  PubMed  Google Scholar 

  37. Tamaki S, Nakamura Y, Tsujita Y, et al: Polymorphism of the angiotensin converting enzyme gene and blood pressure in a Japanese general population (the Shigaraki Study). Hypertens Res 2002; 25: 843–848.

    Article  CAS  PubMed  Google Scholar 

  38. Matsubara M : Genetic determination of human essential hypertension. Tohoku J Exp Med 2000; 192: 19–33.

    Article  CAS  PubMed  Google Scholar 

  39. Zaman MM, Yoshiike N, Date C, et al: Angiotensin converting enzyme genetic polymorphism is not associated with hypertension in a cross-sectional sample of a Japanese population: the Shibata Study. J Hypertens 2001; 19: 47–53.

    Article  CAS  PubMed  Google Scholar 

  40. Turner ST, Boerwinkle E, Sing CF : Context-dependent associations of the ACE I/D polymorphism with blood pressure. Hypertension 1999; 34: 773–778.

    Article  CAS  PubMed  Google Scholar 

  41. O'Donnell CJ, Lindpaintner K, Larson MG, et al: Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study. Circulation 1998; 97: 1766–1772.

    Article  CAS  PubMed  Google Scholar 

  42. Sagnella GA, Rothwell MJ, Onipinla AK, Wicks PD, Cook DG, Cappuccio FP : A population study of ethnic variations in the angiotensin-converting enzyme I/D polymorphism: relationships with gender, hypertension and impaired glucose metabolism. J Hypertens 1999; 17: 657–664.

    Article  CAS  PubMed  Google Scholar 

  43. Schut AF, Sayed-Tabatabaei FA, Witteman JC, et al: Smoking-dependent effects of the angiotensin-converting enzyme gene insertion/deletion polymorphism on blood pressure. J Hypertens 2004; 22: 313–319.

    Article  CAS  PubMed  Google Scholar 

  44. Barlassina C, Schork NJ, Manunta P, et al: Synergistic effect of alpha-adducin and ACE genes causes blood pressure changes with body sodium and volume expansion. Kidney Int 2000; 57: 1083–1090.

    Article  CAS  PubMed  Google Scholar 

  45. Svetkey LP, McKeown SP, Wilson AF : Heritability of salt sensitivity in black Americans. Hypertension 1996; 28: 854–858.

    Article  CAS  PubMed  Google Scholar 

  46. Beeks E, Kessels AG, Kroon AA, van der Klauw MM, de Leeuw PW : Genetic predisposition to salt-sensitivity: a systematic review. J Hypertens 2004; 22: 1243–1249.

    Article  CAS  PubMed  Google Scholar 

  47. Katsuya T, Ishikawa K, Sugimoto K, Rakugi H, Ogihara T : Salt sensitivity of Japanese from the viewpoint of gene polymorphism. Hypertens Res 2003; 26: 521–525.

    Article  PubMed  Google Scholar 

  48. de la Sierra A, Lluch MM, Coca A, et al: Fluid, ionic and hormonal changes induced by high salt intake in salt-sensitive and salt-resistant hypertensive patients. Clin Sci (Lond) 1996; 91: 155–161.

    Article  CAS  Google Scholar 

  49. Engeli S, Gorzelniak K, Kreutz R, Runkel N, Distler A, Sharma AM : Co-expression of renin-angiotensin system genes in human adipose tissue. J Hypertens 1999; 17: 555–560.

    Article  CAS  PubMed  Google Scholar 

  50. He J, Ogden LG, Vupputuri S, Bazzano LA, Loria C, Whelton PK : Dietary sodium intake and subsequent risk of cardiovascular disease in overweight adults. JAMA 1999; 282: 2027–2034.

    Article  CAS  PubMed  Google Scholar 

  51. Strazzullo P, Iacone R, Iacoviello L, et al: Genetic variation in the renin-angiotensin system and abdominal adiposity in men: the Olivetti Prospective Heart Study. Ann Intern Med 2003; 138: 17–23.

    Article  CAS  PubMed  Google Scholar 

  52. Riera-Fortuny C, Real JT, Chaves FJ, et al: The relation between obesity, abdominal fat deposit and the angiotensin-converting enzyme gene I/D polymorphism and its association with coronary heart disease. Int J Obes Relat Metab Disord 2005; 29: 78–84.

    Article  CAS  Google Scholar 

  53. Cleveland LE, Escobar AJ, Lutz SM, Welsh SO : Method for identifying differences between existing food intake patterns and patterns that meet nutrition recommendations. J Am Diet Assoc 1993; 93: 556–560, 563.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan

    Ling Zhang, Koichi Miyaki, Jungo Araki, Yixuan Song, Tomomi Kimura & Masaaki Muramatsu

  2. Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Tokyo, Japan

    Koichi Miyaki & Kazuyuki Omae

Authors
  1. Ling Zhang
    View author publications

    Search author on:PubMed Google Scholar

  2. Koichi Miyaki
    View author publications

    Search author on:PubMed Google Scholar

  3. Jungo Araki
    View author publications

    Search author on:PubMed Google Scholar

  4. Yixuan Song
    View author publications

    Search author on:PubMed Google Scholar

  5. Tomomi Kimura
    View author publications

    Search author on:PubMed Google Scholar

  6. Kazuyuki Omae
    View author publications

    Search author on:PubMed Google Scholar

  7. Masaaki Muramatsu
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Masaaki Muramatsu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, L., Miyaki, K., Araki, J. et al. Interaction of Angiotensin I–Converting Enzyme Insertion-Deletion Polymorphism and Daily Salt Intake Influences Hypertension in Japanese Men. Hypertens Res 29, 751–758 (2006). https://doi.org/10.1291/hypres.29.751

Download citation

  • Received: 27 January 2006

  • Accepted: 19 June 2006

  • Issue date: 01 October 2006

  • DOI: https://doi.org/10.1291/hypres.29.751

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Keywords

  • angiotensin I–converting enzyme
  • polymorphism
  • salt sensitivity
  • hypertension
  • gene-environment interaction

This article is cited by

  • Hypertension and longevity: role of genetic polymorphisms in renin-angiotensin-aldosterone system and endothelial nitric oxide synthase

    • Alda Pereira da Silva
    • Andreia Matos
    • Manuel Bicho

    Molecular and Cellular Biochemistry (2019)

  • Signaling pathway genes for blood pressure, folate and cholesterol levels among hypertensives: an epistasis analysis

    • L K Wei
    • S Menon
    • S H Gan

    Journal of Human Hypertension (2015)

  • High salt intake as a multifaceted cardiovascular disease: new support from cellular and molecular evidence

    • Marcelo Perim Baldo
    • Sérgio Lamêgo Rodrigues
    • José Geraldo Mill

    Heart Failure Reviews (2015)

  • Association of the Catechol-O-Methyl Transferase Gene Val158Met Polymorphism With Blood Pressure and Prevalence of Hypertension: Interaction With Dietary Energy Intake

    • N. C. Htun
    • K. Miyaki
    • M. Muramatsu

    American Journal of Hypertension (2011)

  • Genetics of Salt-Sensitive Hypertension

    • Hironobu Sanada
    • John E. Jones
    • Pedro A. Jose

    Current Hypertension Reports (2011)

Download PDF

Advertisement

Explore content

  • Research articles
  • Reviews & Analysis
  • News & Comment
  • Current issue
  • Collections
  • Sign up for alerts
  • RSS feed

About the journal

  • Journal Information
  • Open Access Fees and Funding
  • Guide to Authors
  • About the Editors
  • Message from Editors
  • Call for Paper
  • Contact
  • About the Partner
  • For Advertisers
  • Subscribe
  • Showcase of Graphical Abstracts on Hypertension Research

Publish with us

  • For Authors & Referees
  • Language editing services
  • Open access funding
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

Hypertension Research (Hypertens Res)

ISSN 1348-4214 (online)

ISSN 0916-9636 (print)

nature.com sitemap

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2025 Springer Nature Limited