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CLINICAL STUDY: RISK FACTORS

Association of angiotensinogen m235t and a(-6)g gene polymorphisms with coronary heart disease with independence of essential hypertension: the procagene study

José C. Rodríguez-Pérez, MD, PhD^*, Francisco Rodríguez-Esparragón, PhD^*, Octavio Hernández-Perera, PhD^*, Aránzazu Anabitarte, RN^*, Antonio Losada, MD^*, Alfonso Medina, MD, PhD^*, Enrique Hernández, MD, PhD^*, Dolores Fiuza, MD^*, Octavio Avalos, MD, PhD^*, Carla Yunis, MD, Carlos M. Ferrario, MD for the PROCAGENE Study Investigators

^* Research Unit, Hemodynamic-Cardiology and Nephrology Services, Hospital de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Canary Islands, Spain
Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA

Manuscript received March 3, 2000; revised manuscript received December 14, 2000, accepted January 17, 2001.

Reprint requests and correspondence: Dr. José C. Rodríguez-Pérez, Research Unit and Nephrology Service, Hospital de Gran Canaria Dr. Negrín, Bco. de la Ballena s/n, 35020 Las Palmas de Gran Canaria, Spain
jcrodrig{at}invest.hpino.rcanaria.es

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.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   AGT = angiotensinogen   BMI = body mass index   BP = blood pressure   CHD = coronary heart disease   CI = confidence interval   CVD = cardiovascular disease   I/D = insertion/deletion   Lp (a) = lipoprotein (a)   MI = myocardial infarction   OR = odds ratio   PCR = polymerase chain reaction   PROCAGENE = Prospective Cardiac Gene Study

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