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.

  • Original Article
  • Published:

The effect of genetic variation in angiotensinogen on serum levels and blood pressure: a comparison of Nigerians and US blacks

Journal of Human Hypertension volume 20, pages 882–887 (2006)Cite this article

Abstract

Molecular variants of angiotensinogen (AGT) have been associated with AGT level and hypertension (HT). However, results from reported studies vary considerably between- and within-studied populations. We performed association analysis of AGT gene variants with AGT levels and HT in samples of African descent families, including 595 Nigerians and 901 African Americans. We evaluated association using haplotypes defined by a set of single-nucleotide polymorphisms selected from a previous detailed study of the gene haplotype structure. In the sample of Nigerian families, AGT haplotype H1 was associated with high plasma level. Results were not significant for blood pressure (BP) or HT. For the African-American population, we found significant association between low plasma AGT level and haplotype H7. Furthermore, we found weak associations of H1 with hypertensive status and H7 with low systolic BP. However, no significant association between H1 and high plasma level was found. We conclude that the two distantly related haplotypes, H1 and H7, are associated, but have opposite effects on the phenotypes in two populations of African origin.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Cusi D, Macciardi F, Barlassina C . Angiotensinogen gene polymorphism, again? J Hypertens 2003; 21 (10): 1815–1818.

    Article  CAS  Google Scholar 

  2. Zhu X, Bouzerkri N, Southam L, Cooper RS, Adeyemo A, Mckenzie CA et al. Linkage and association analysis of angiotensin I-converting enzyme (ACE)-gene polymorphisms with ACE concentration and blood pressure. Am J Hum Genet 2001; 68 (5): 1139–1148.

    Article  CAS  Google Scholar 

  3. Jeunemaitre X, Soubrier F, Kotelevtsev YV, Lifton RP, Williams CS, Charru A et al. Molecular basis of human hypertension: role of angiotensinogen. Cell 1992; 71 (1): 169–180.

    Article  CAS  Google Scholar 

  4. Iso H, Harada S, Shimamot T, Sato S, Kitamura A, Sankai T et al. Angiotensinogen T174M and M235T variants, sodium intake and hypertension among non-drinking, lean Japanese men and women. J Hypertens 2000; 18 (9): 1197–1206.

    Article  CAS  Google Scholar 

  5. Sato N, Katsuya T, Nakagawa T, Ishikawa K, Fu Y, Asai T et al. Nine polymorphisms of angiotensinogen gene in the susceptibility to essential hypertension. Life Sci 2000; 68 (3): 259–272.

    Article  CAS  Google Scholar 

  6. Sethi AA, Nordestgaard BG, Agerholm-Larsen B, Frandsen E, Jensen G, Tybjaerg-Hansen A . Angiotensinogen polymorphisms and elevated blood pressure in the general population: the Copenhagen City Heart Study. Hypertension 2001; 37 (3): 875–881.

    Article  CAS  Google Scholar 

  7. Svetkey LP, Moore TJ, Simons-Morton DG, Appel LJ, Bray GA, Sacks FM et al. Angiotensinogen genotype and blood pressure response in the Dietary Approaches to Stop Hypertension (DASH) study. J Hypertens 2001; 19 (11): 1949–1956.

    Article  CAS  Google Scholar 

  8. Pereira AC, Mota GFA, Cunha RS, Herbenhoff FL, Mill JG, Krieger JE et al. Angiotensinogen 235T allele dosage is associated with blood pressure phenotype. Hypertension 2003; 41: 25–30.

    Article  CAS  Google Scholar 

  9. Bengtsson K, Orho-Melander M, Lindbland U, Melander O, Bog-Hansen E, Ranstam L et al. Polymorphism in the angiotensin converting enzyme but not in the angiotensinogen gene is associated with hypertension and type 2 diabetes: the Skaraborg Hypertension and diabetes project. J Hypertens 1999; 17 (11): 1569–1575.

    Article  CAS  Google Scholar 

  10. Niu T, Chen C, Yang J, Wang B, Wang Z, Schork N et al. Blood pressure and the T174M and M235T polymorphisms of the angiotensinogen gene. Ann Epidemiol 1999; 9 (4): 245–253.

    Article  CAS  Google Scholar 

  11. Taittonen L, Uhari M, Kontula K, Kainulainen K, Miettinen H, Turtinen J et al. Angiotensin converting enzyme gene insertion/deletion polymorphism, angiotensinogen gene polymorphisms, family history of hypertension, and childhood blood pressure. American Journal of Hypertension. J Am Soc Hypertens 1999; 12 (9 Part 1): 858–866.

    Article  CAS  Google Scholar 

  12. Kato N, Sugiyama T, Morita H, Kurihara H, Furukawa T, Isshiki T et al. Comprehensive analysis of the rennin–angiotensin gene polymorphisms with relation to hypertension in the Japanese. J Hypertens 2000; 18 (8): 1025–1032.

    Article  CAS  Google Scholar 

  13. Larson N, Hutchinson R, Boerwinkle E . Lack of association of 3 functional gene variants with hypertension in African Americans. Hypertension 2000; 35 (6): 1297–1300.

    Article  CAS  Google Scholar 

  14. Province MA, Boerwinkle E, Chakravarti A, Cooper R, Fornage M, Leppert M et al. Lack of association of the angiotensinogen-6 polymorphism with blood pressure levels in the comprehensive NHLBI family blood pressure program. National Heart, Lung and Blood Institute. J Hypertens 2000; 18 (7): 867–876.

    Article  CAS  Google Scholar 

  15. Fejerman L, Bouzekri N, Wu X, Adeyemo A, Luke A, Zhu X et al. Association between evolutionary history of angiotensinogen haplotypes and plasma levels. Hum Genet 2004; 115 (5): 310–318.

    CAS  PubMed  Google Scholar 

  16. Falush D, Stephens M, Pritchard JK . Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies. Genetics 2003; 164: 1567–1587.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Ataman SL, Cooper RS, Rotimi CN, McGee D, Osotimehin B, Kadiri S et al. Standardization of blood pressure measurement in an international collaborative study. J Clin Epidemiol 1996; 49: 869–877.

    Article  CAS  Google Scholar 

  18. Cooper RS, Rotimi CN, Ataman SL, McGee D, Osotimehin B, Kadiri S et al. The prevalence of hypertension in seven populations of West African origin. Am J Public Health 1997; 87: 160–168.

    Article  CAS  Google Scholar 

  19. Rotimi C, Cooper R, Ogunbiyi O, Morrison L, Ladipo M, Tewksbury D et al. Hypertension, serum angiotensinogen, and molecular variants of the angiotensinogen gene among Nigerians. Circulation 1997; 95 (10): 2348–2350.

    Article  CAS  Google Scholar 

  20. Plummer S, Morgan L, Kalsheker N . SNPs at the 3′ end of the angiotensinogen gene define two haplotypes associated with the common 235Met variant. Am J Hum Genet 2002; 71: 443–444.

    Article  CAS  Google Scholar 

  21. SAS Version 8.2. SAS Institute: Cary, NC.

  22. Almasy L, Blangero J . Multipoint quantitative-trait analysis in general pedigrees. Am J Hum Genet 1998; 62: 1198–1211.

    Article  CAS  Google Scholar 

  23. Abecasis GR, Cherny SS, Cookson WO, Cardon LR . Merlin – rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet 2002; 30 (1): 97–101.

    Article  CAS  Google Scholar 

  24. Horvath S, Xu X, Laird NM . The family based association test method: strategies for studying general genotype–phenotype associations. Eur J Hum Genet 2001; 9: 301–306.

    Article  CAS  Google Scholar 

  25. Horvath S, Xu X, Lake SL, Silverman EK, Weiss ST, Laird NM . Family-based test for associating haplotypes with general phenotype data: application to asthma genetics. Genet Epidemiol 2004; 26: 61–69.

    Article  Google Scholar 

  26. Nyholt DR . A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am J Hum Genet 2004; 74 (4): 765–769.

    Article  CAS  Google Scholar 

  27. Nakajima T, Wooding S, Sakagami T, Emi M, Tokunaga K, Tamiya G et al. Natural selection and population history in the human angiotensinogen gene (AGT): 736 complete AGT sequences in chromosomes from around the world. Am J Hum Genet 2004; 74 (5): 898–916.

    Article  CAS  Google Scholar 

  28. Sethi AA, Nordestgaard BG, Gronholdt ML, Steffensen R, Jensen G, Tybjaerg-Hansen A . Angiotensinogen single nucleotide polymorphisms, elevated blood pressure, and risk of cardiovascular disease. Hypertension 2003; 41: 1202–1211.

    Article  CAS  Google Scholar 

  29. Wu X, Luke A, Rieder M, Lee K, Toth EJ, Nickerson D et al. An association study of angiotensinogen polymorphisms with serum level and hypertension in an African-American population. J Hypertens 2003; 21: 1847–1852.

    Article  CAS  Google Scholar 

  30. Poston WS, Pavlik VN, Hyman DJ, Ogbonnaya K, Hanis CL, Haddock CK et al. Genetic bottlenecks, perceived racism, and hypertension risk among African Americans and first-generation African immigrants. J Hum Hypertens 2001; 15 (5): 341–351.

    Article  CAS  Google Scholar 

  31. Rotimi C, Morrison L, Cooper R, Oyejide C, Effiong E, Ladipo M et al. Angiotensinogen gene in human hypertension: lack of an association of the 235T allele among African Americans. Hypertension 1994; 24: 591–594.

    Article  CAS  Google Scholar 

  32. Kumar A, Li Y, Patil S, Jain S . A haplotype of the angiotensinogen gene is associated with hypertension in African Americans. Clin Exp Pharmacol Physiol 2005; 32 (5–6): 495–502.

    Article  CAS  Google Scholar 

  33. Markovic D, Tang X, Guruju M, Levenstien MA, Hoh J, Kumar A et al. Association of angiotensinogen gene polymorphisms with essential hypertension in African Americans and Caucasians. Hum Hered 2005; 60 (2): 89–96.

    Article  CAS  Google Scholar 

  34. Jain S, Tang X, Narayanan CS, Agarwal Y, Peterson SM, Brown CD et al. Angiotensinogen gene polymorphism at −217 affects basal promoter activity and is associated with hypertension in African-Americans. J Biol Chem 2002; 277 (39): 36889–36896.

    Article  CAS  Google Scholar 

  35. Inoue I, Nakajima T, Williams CS, Quackenbush J, Puryear R, Powers M et al. A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro. J Clin Invest 1997; 99 (7): 1786–1797.

    Article  CAS  Google Scholar 

  36. Yanai K, Nibu Y, Murakami K, Fukamizu A . A cis-acting DNA element located between TATA box and transcription initiation site is critical in response to regulatory sequences in human angiotensinogen gene. J Biol Chem 1996; 271 (27): 15981–15986.

    Article  CAS  Google Scholar 

  37. Denton D, Weisinger R, Mundy NI, Wickings EJ, Dixson A, Moison P et al. The effect of increased salt intake on blood pressure of chimpanzees. Nat Med 1995; 1 (10): 1009–1016.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was support by research grants from the NHLBI (HL45508 and HL53353) and the Donald W Reynolds Cardiovascular Clinical Research Center from the University of Texas Southwestern Medical School.

Author information

Authors and Affiliations

  1. Department of Biological Anthropology, University of Oxford, Oxford, UK

    L Fejerman

  2. Department of Preventive Medicine and Epidemiology, Loyola University Medical Center, Maywood, IL, USA

    X Wu, A Luke, X Zhu, C Hicks & R S Cooper

  3. Department of Pediatrics, University College Hospital, University of Ibadan, Ibadan, Nigeria

    A Adeyemo

Authors
  1. L Fejerman
    View author publications

    Search author on:PubMed Google Scholar

  2. X Wu
    View author publications

    Search author on:PubMed Google Scholar

  3. A Adeyemo
    View author publications

    Search author on:PubMed Google Scholar

  4. A Luke
    View author publications

    Search author on:PubMed Google Scholar

  5. X Zhu
    View author publications

    Search author on:PubMed Google Scholar

  6. C Hicks
    View author publications

    Search author on:PubMed Google Scholar

  7. R S Cooper
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to L Fejerman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fejerman, L., Wu, X., Adeyemo, A. et al. The effect of genetic variation in angiotensinogen on serum levels and blood pressure: a comparison of Nigerians and US blacks. J Hum Hypertens 20, 882–887 (2006). https://doi.org/10.1038/sj.jhh.1002077

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/sj.jhh.1002077

Keywords

This article is cited by

Search

Advanced search

Quick links