Association of angiotensinogen M235T and A(-6)G gene polymorphisms with coronary heart disease with independence of essential hypertension: the PROCAGENE study. Prospective Cardiac Gene

J Am Coll Cardiol. 2001 May;37(6):1536-42. doi: 10.1016/s0735-1097(01)01186-x.


Objectives: We examined the relationship between the angiotensinogen (AGT) gene M235T polymorphism, the variant promoter of the AGT gene A(-6)G and the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and coronary heart disease (CHD) in native Gran Canaria Island habitants, who have the highest rates of CHD in Spain.

Background: Some studies subject that the ACE (I/D) polymorphism could be associated with CHD, while AGT (M235T) has been related to essential hypertension.

Methods: We studied 304 subjects with angiographic evidence of coronary artery disease and a clinical diagnosis of myocardial infarction or unstable angina and 315 age- and gender-matched controls. Blood was drawn and DNA extracted. Angiotensin-converting enzyme (I/D) gene polymorphism was analyzed by polymerase chain reaction (PCR) and AGT gene polymorphisms by restriction fragment length polymorphism-PCR and mutagenically-separated PCR.

Results: The ACE (I/D) polymorphism showed no association with CHD, whereas the frequency distribution of AGT (M235T) genotypes among patients and controls (235T: 29.1% and 19.0%; M235T: 48.5% and 50.2%; M235: 22.4% and 30.8%, respectively) was statistically different (p = 0.005) and not related to the presence of essential hypertension. Similar results were observed with the AGT A(-6)G polymorphism. In multiple logistic regression analysis, CHD odds ratio associated with 235T and M235 homozygotes were 1.7 (1.1 to 2.6) and 0.54 (0.36 to 0.82), respectively.

Conclusions: This study shows that genetic variation of the AGT (M235T), but not the ACE (I/D), genotypes contributes to the presence of CHD independently of blood pressure profile in a subset of the Spanish population with a high prevalence of cardiovascular disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angina, Unstable / blood
  • Angina, Unstable / diagnosis
  • Angina, Unstable / epidemiology
  • Angina, Unstable / genetics*
  • Angiotensinogen / genetics*
  • Case-Control Studies
  • Coronary Disease / blood
  • Coronary Disease / diagnostic imaging
  • Coronary Disease / epidemiology
  • Coronary Disease / genetics*
  • Female
  • Gene Deletion*
  • Gene Frequency / genetics
  • Genetic Markers / genetics
  • Genetic Variation / genetics*
  • Genotype
  • Homozygote
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Mutagenesis, Insertional / genetics*
  • Myocardial Infarction / blood
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / genetics*
  • Odds Ratio
  • Peptidyl-Dipeptidase A / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / genetics*
  • Polymorphism, Restriction Fragment Length
  • Prevalence
  • Promoter Regions, Genetic / genetics
  • Radiography
  • Renin-Angiotensin System / genetics
  • Risk Factors
  • Spain / epidemiology


  • Genetic Markers
  • Angiotensinogen
  • Peptidyl-Dipeptidase A