Association of angiotensinogen M235T and A(-6)G gene polymorphisms with coronary heart disease with independence of essential hypertension: The PROCAGENE study

OBJECTIVES We examined the relationship between the angiotensinogen (AGT) g ene M235T polymorphism, the variant promote; of the AGT gene A(-6)G and the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorp hism and coronary heart disease (CHD) in native Gran Canaria Island habitan ts, who have the highest rates of CHD in Spain. BACKGROUND Some studies subject that the ACE (I/D) polymorphism could be as sociated with CHD, while AGT (M235T) has been related to essential hyperten sion. METHODS We studied 304 subjects with angiographic evidence of coronary arte ry disease and a clinical diagnosis of myocardial infarction or unstable an gina and 315 age- and gender-matched controls. Blood was drawn and DNA extr acted. Angiotensin-converting enzyme (I/D) gene polymorphism was analyzed b y polymerase chain reaction (PCR) and AGT gene polymorphisms by restriction fragment length polymorphism-PCR and mutagenically-separated PCR. RESULTS The ACE (I/D) polymorphism shelved no association with CHD, whereas the frequency distribution of AGT (M235T) genotypes among patients and con trols (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 odd ratio associated with 235T and M235 homozygotes were 1.7 (1.1 to 2.6) a nd 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 independent ly of blood pressure profile in a subset of the Spanish population with a h igh prevalence of cardiovascular disease. (J Am Coll Cardiol 2001;37:1536-4 2) (C) 2001 by the American College of Cardiology.