Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1998 Jan 1;101(1):188–194. doi: 10.1172/JCI119876

Angiotensinogen gene and hypertension in Chinese.

T Niu 1, X Xu 1, J Rogus 1, Y Zhou 1, C Chen 1, J Yang 1, Z Fang 1, C Schmitz 1, J Zhao 1, V S Rao 1, K Lindpaintner 1
PMCID: PMC508555  PMID: 9421481

Abstract

The renin-angiotensin system plays a major role in regulating blood pressure and maintaining electrolyte and volume homeostasis. Previously, the angiotensinogen gene, which encodes the key substrate for renin within this system, has been reported linked to and associated with essential hypertension in White Europeans, African-Caribbeans, and Japanese. Therefore, we investigated whether the angiotensinogen gene might be similarly implicated in the pathogenesis of essential hypertension in Chinese by carrying out linkage analysis in 310 hypertensive sibling pairs. Genotypes for two diallelic DNA polymorphisms observed at amino acid residues 174 (T174M) and 235 (M235T) within the coding sequence and for two highly informative dinucleotide (GT)-repeat sequences (one in the 3' flanking region, and one at a distance of 6.1 cM from the gene) were determined. Affected sibpair analysis conducted according to three different algorithms (S.A.G.E./SIBPAL, MAPMAKER/ SIBS, and APM methods) revealed no evidence for linkage of the angiotensinogen gene to hypertension. Our data indicate that molecular variants of this gene do not appear to contribute materially to the pathogenesis of primary hypertension among Chinese (a notion supported by concomitant, direct estimates of power), and that the disease relevance of this gene may vary therefore depending on ethnicity.

Full Text

The Full Text of this article is available as a PDF (167.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Caulfield M., Lavender P., Farrall M., Munroe P., Lawson M., Turner P., Clark A. J. Linkage of the angiotensinogen gene to essential hypertension. N Engl J Med. 1994 Jun 9;330(23):1629–1633. doi: 10.1056/NEJM199406093302301. [DOI] [PubMed] [Google Scholar]
  2. Caulfield M., Lavender P., Newell-Price J., Farrall M., Kamdar S., Daniel H., Lawson M., De Freitas P., Fogarty P., Clark A. J. Linkage of the angiotensinogen gene locus to human essential hypertension in African Caribbeans. J Clin Invest. 1995 Aug;96(2):687–692. doi: 10.1172/JCI118111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Gross-Bellard M., Oudet P., Chambon P. Isolation of high-molecular-weight DNA from mammalian cells. Eur J Biochem. 1973 Jul 2;36(1):32–38. doi: 10.1111/j.1432-1033.1973.tb02881.x. [DOI] [PubMed] [Google Scholar]
  4. Hata A., Namikawa C., Sasaki M., Sato K., Nakamura T., Tamura K., Lalouel J. M. Angiotensinogen as a risk factor for essential hypertension in Japan. J Clin Invest. 1994 Mar;93(3):1285–1287. doi: 10.1172/JCI117083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Havlik R. J., Garrison R. J., Feinleib M., Kannel W. B., Castelli W. P., McNamara P. M. Blood pressure aggregation in families. Am J Epidemiol. 1979 Sep;110(3):304–312. doi: 10.1093/oxfordjournals.aje.a112815. [DOI] [PubMed] [Google Scholar]
  6. Higgins M. W., Keller J. B., Metzner H. L., Moore F. E., Ostrander L. D., Jr Studies of blood pressure in Tecumseh, Michigan. II. Antecedents in childhood of high blood pressure in young adults. Hypertension. 1980 Jul-Aug;2(4 Pt 2):117–123. [PubMed] [Google Scholar]
  7. Holmans P. Asymptotic properties of affected-sib-pair linkage analysis. Am J Hum Genet. 1993 Feb;52(2):362–374. [PMC free article] [PubMed] [Google Scholar]
  8. Jeunemaitre X., Soubrier F., Kotelevtsev Y. V., Lifton R. P., Williams C. S., Charru A., Hunt S. C., Hopkins P. N., Williams R. R., Lalouel J. M. Molecular basis of human hypertension: role of angiotensinogen. Cell. 1992 Oct 2;71(1):169–180. doi: 10.1016/0092-8674(92)90275-h. [DOI] [PubMed] [Google Scholar]
  9. Kruglyak L., Lander E. S. Complete multipoint sib-pair analysis of qualitative and quantitative traits. Am J Hum Genet. 1995 Aug;57(2):439–454. [PMC free article] [PubMed] [Google Scholar]
  10. Lander E., Kruglyak L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet. 1995 Nov;11(3):241–247. doi: 10.1038/ng1195-241. [DOI] [PubMed] [Google Scholar]
  11. Levine R. S., Hennekens C. H., Perry A., Cassady J., Gelband H., Jesse M. J. Genetic variance of blood pressure levels in infant twins. Am J Epidemiol. 1982 Nov;116(5):759–764. doi: 10.1093/oxfordjournals.aje.a113465. [DOI] [PubMed] [Google Scholar]
  12. Lindpaintner K., Pfeffer M. A., Kreutz R., Stampfer M. J., Grodstein F., LaMotte F., Buring J., Hennekens C. H. A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease. N Engl J Med. 1995 Mar 16;332(11):706–711. doi: 10.1056/NEJM199503163321103. [DOI] [PubMed] [Google Scholar]
  13. Miller S. A., Dykes D. D., Polesky H. F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 Feb 11;16(3):1215–1215. doi: 10.1093/nar/16.3.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Risch N. Linkage strategies for genetically complex traits. I. Multilocus models. Am J Hum Genet. 1990 Feb;46(2):222–228. [PMC free article] [PubMed] [Google Scholar]
  15. Risch N. Linkage strategies for genetically complex traits. II. The power of affected relative pairs. Am J Hum Genet. 1990 Feb;46(2):229–241. [PMC free article] [PubMed] [Google Scholar]
  16. Risch N. Linkage strategies for genetically complex traits. III. The effect of marker polymorphism on analysis of affected relative pairs. Am J Hum Genet. 1990 Feb;46(2):242–253. [PMC free article] [PubMed] [Google Scholar]
  17. Rotimi C., Morrison L., Cooper R., Oyejide C., Effiong E., Ladipo M., Osotemihen B., Ward R. Angiotensinogen gene in human hypertension. Lack of an association of the 235T allele among African Americans. Hypertension. 1994 Nov;24(5):591–594. doi: 10.1161/01.hyp.24.5.591. [DOI] [PubMed] [Google Scholar]
  18. Russ A. P., Maerz W., Ruzicka V., Stein U., Gross W. Rapid detection of the hypertension-associated Met235-->Thr allele of the human angiotensinogen gene. Hum Mol Genet. 1993 May;2(5):609–610. doi: 10.1093/hmg/2.5.609. [DOI] [PubMed] [Google Scholar]
  19. Sander A., Kennedy M. A., Rayner J. C., Murray J. C. Dinucleotide repeat polymorphism for HLX1 gene. Hum Mol Genet. 1994 Jan;3(1):219–219. doi: 10.1093/hmg/3.1.219-a. [DOI] [PubMed] [Google Scholar]
  20. Schork N. J., Nath S. P., Lindpaintner K., Jacob H. J. Extensions to quantitative trait locus mapping in experimental organisms. Hypertension. 1996 Dec;28(6):1104–1111. [PubMed] [Google Scholar]
  21. Weeks D. E., Lange K. A multilocus extension of the affected-pedigree-member method of linkage analysis. Am J Hum Genet. 1992 Apr;50(4):859–868. [PMC free article] [PubMed] [Google Scholar]
  22. Weeks D. E., Lange K. The affected-pedigree-member method of linkage analysis. Am J Hum Genet. 1988 Feb;42(2):315–326. [PMC free article] [PubMed] [Google Scholar]
  23. Xu X., Niu T., Christiani D. C., Weiss S. T., Zhou Y., Chen C., Yang J., Fang Z., Jiang Z., Liang W. Environmental and occupational determinants of blood pressure in rural communities in China. Ann Epidemiol. 1997 Feb;7(2):95–106. doi: 10.1016/s1047-2797(96)00126-3. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES