Association of angiotensinogen gene T235 variant with increased risk of coronary heart disease.

Journal Article (Journal Article)

Several genes, including some encoding components of the renin angiotensin system, are associated with the risk of cardiovascular diseases. There have been reports linking a homozygous deletion allele of the angiotensin converting enzyme (ACE) gene (DD) with an increased risk of myocardial infarction, and some variants of the angiotensinogen gene with an increased risk of hypertension. In a case-control study of a caucasian population from New Zealand, we examined the associations with coronary heart disease (CHD) of ACE DD and of a mis-sense mutation with methionine to threonine aminoacid substitution at codon 235 in the angiotensinogen gene (T235). We studied 422 patients (mean age 62 years, 81% male) with documented CHD (50% with myocardial infarction) and 406 controls without known CHD (frequency-matched to cases by age and sex). Risk factors for CHD were assessed by standard questionnaire, physical examination, and blood tests. Genomic DNA from leucocytes was analysed for various ACE and angiotensinogen alleles. Angiotensinogen T235 homozygotes were at significantly increased risk of CHD generally (odds ratio 1.7, 2 p = 0.008) and of myocardial infarction specifically (1.8, 2 p = 0.009). Adjustment for several risk factors increased the estimate of CHD risk associated with this allele to 2.6 (2 p < 0.001) and the estimate for myocardial infarction risk to 3.4 (2 p < 0.001). By contrast, there was no evidence of a significant increase in the risk of CHD or myocardial infarction among individuals with ACE DD. We conclude that the T235 polymorphism of the angiotensinogen gene is an independent risk factor, which carries an approximately two-fold increased risk of CHD. In this study, however, ACE DD was not associated with any detectable increase in CHD risk.

Full Text

Duke Authors

Cited Authors

  • Katsuya, T; Koike, G; Yee, TW; Sharpe, N; Jackson, R; Norton, R; Horiuchi, M; Pratt, RE; Dzau, VJ; MacMahon, S

Published Date

  • June 24, 1995

Published In

Volume / Issue

  • 345 / 8965

Start / End Page

  • 1600 - 1603

PubMed ID

  • 7783537

International Standard Serial Number (ISSN)

  • 0140-6736

Digital Object Identifier (DOI)

  • 10.1016/s0140-6736(95)90115-9


  • eng

Conference Location

  • England