Aldosterone synthase alleles and cardiovascular phenotype in young adults.

The C(-344)T promoter polymorphism of the human aldosterone synthase (CYP11B2) gene has been associated with hypertension and cardiac hypertrophy, but there were contrasting data. We analysed the genotype/phenotype associations between this polymorphism and cardiovascular variables in a young adult population, where interactions among genes, gene-environment, and acquired ageing-related organ damage are reduced. Anthropometric measurements, blood pressure, heart rate, left ventricular variables (by echocardiography), and carotid artery wall intimal-media thickness (by high-resolution sonography and digitalized morphometry) were taken in 420 white Caucasian students (mean age 23.5 years, s.d. 2.5 years). CYP11B2 alleles were detected by genomic polymerase chain reaction followed by digestion. Taking into account the three possible models of inheritance, we found no differences in the considered variables, except for an independent effect of the C(-344) allele on SBP in males (TT 125.6 (1.6), TC 128.4 (1.2) and CC 130.5 (2.2), mmHg, media (ES), P=0.03), and on interventricular septum thickness in diastole in females (CC 6.98 (0.12) vs TT 6.87 (0.09) and TC 6.87 (0.07), mmHg, P<0.01), in the codominant model. In conclusion, the CYP11B2 C(-344)T polymorphism appears to have a slight role in the cardiovascular phenotype of young healthy adults, even if these genotype/phenotype relationships might change with ageing.

Cardiovascular phenotype of young adults and angiotensinogen alleles.

OBJECTIVES AND DESIGN: Angiotensinogen (AGT) gene variants influence angiotensinogen plasma levels in children and young adults. The angiotensinogen promoter (-6)A variant facilitates gene transcription in human tissues and it has been associated with high blood pressure in older adults. A young adult population can be used as a model to study genotype/phenotype associations between AGT (-6) variants and cardiovascular variables. METHODS AND RESULTS: Anthropometric measurements, blood pressure and heart rate were taken in 422 white Caucasian students (mean age 23.5 years, SD 2.5 years). Family history for hypertension, physical activity and smoking history were evaluated. Left ventricular variables were measured by echocardiography. Carotid artery wall intimal-media thickness (IMT) was measured by high resolution sonography and digitalized morphometry. The AGT G(-6)A alleles were evaluated by mutagenically separated polymerase chain reaction controlled by direct sequencing. No significant associations were found between angiotensinogen genotype and blood pressure, cardiac variables [except for deceleration time in females which increased with the number of (-6)A alleles] and IMT. Allele frequencies were similar between the first and third tertile of blood pressure and left ventricular mass, and were also similar between negative or positive family history for hypertension (the last group having significantly higher systolic blood pressure in males, P = 0.04 and diastolic blood pressure in females, P < 0.01). Moreover, no relevant interaction on the cardiovascular variables was found between AGT genotype and body mass index. CONCLUSIONS: The angiotensinogen G(-6)A variants do not affect cardiovascular parameters in young adults, but an effect of this polymorphism on cardiovascular phenotype (and hypertension) in older adults cannot be excluded. Additional factors, associated with ageing, should be present to unleash the supposed unfavourable potential of the (-6)A angiotensinogen variant.

Angiotensin converting enzyme gene polymorphism and carotid atherosclerosis in a low-risk population.

OBJECTIVES: Angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism has been shown to be an independent risk factor for myocardial infarction and other cardiovascular diseases. The aim of the study was to investigate the relationship between ACE genotype and carotid atherosclerosis evaluated by ultrasonography. PATIENTS AND METHODS: ACE I/D polymorphism was determined in 240 low-risk patients (mean age 53.6 +/- 7 years) in relation to traditional risk factors and the degree of carotid atherosclerosis. Intimal-medial thickness was measured at the level of the common carotid artery, bifurcation and internal carotid on both sides. Patients were defined as normal (n = 47, intimal-medial thickness <1.0 mm), thickened (n = 56, intimal-medial thickness > or = 1.0 and < or = 1.3 mm in the thickest wall) or with an atherosclerotic plaque (n = 137, intimal-medial thickness >1.3 mm for at least one level of examination). Age, sex, body mass index, blood pressure levels and prevalence of other risk factors were similar in the three groups. I/D polymorphism was determined by polymerase chain reaction using specific primers and genomic DNA from leukocytes as template. Plasma ACE levels, plasma renin activity and plasma aldosterone were evaluated in all patients by standard procedures. RESULTS: No significant differences were found in humoral parameters, ACE, genotype distribution and the corresponding allele frequency among the three groups of patients. Only ACE plasma levels were significantly higher in the DD and ID genotypes compared with the II genotype (DD 14.27 +/- 5.05 IU/ml, ID 12.70 +/- 4.31 IU/ml; II 8.04 +/- 3.45 IU/ml). The mean intimal-medial thickness was similar in all three genotypes. CONCLUSION: Although ACE genotype has been shown to be related to coronary atherosclerosis, the present data do not indicate that the DD genotype is associated with carotid atherosclerosis. However, further studies of larger populations are needed to clarify whether genetic ACE polymorphism is associated with carotid atherosclerosis.