CCR polymorphisms and hypertension.
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Adult↗
Biomedical subjects
M Mettimano
Publications and source records attributed to M Mettimano.
Lack of association of CCR gene polymorphisms and left ventricular hypertrophy in essential hypertension.
Left ventricular hypertrophy (LVH) is a major determinant of heart damage. Scientific evidence suggests the influence of genetic factors, but these have yet to be completely clarified. This study investigates a possible relationship between LVH and two chemokine receptor (CCR) gene polymorphisms: CCR5delta32 and CCR264I. Essential hypertensive out-patients (n=118, grade I-II, age 27-54) were recruited from the Catholic University Hypertension Centre. For each subject, clinical data on office blood pressure and M-mode/2D echocardiography were collected. Statistical analysis did not show a significant association between the CCR polymorphisms and LVH in the study population.
Adult↗
Epidemiology of essential hypertension: the role of genetic polymorphism.
Over the past 20 years, the interest of the scientific community was increasingly placed in the field of genetic epidemiology and molecular genetics of blood pressure control. This paper explores references related to essential hypertension, gene and genetic epidemiology indexed in the MedLine health science database during the period 1980-2001. A systematic literature search was performed using selected keywords, such as 'genetic', 'genome' or a combination of words. We considered the study heading and evaluated the time profile of published articles. A total number of 3116 publications was collected and analyzed. Allelic distribution for the most studied polymorphisms of the renin-angiotensin system in different world populations was reviewed and reported together with a detection of their frequency in Italy: essential hypertensive patients (n = 90), healthy unrelated subjects (n = 300). Molecular variants at angiotensinogen (M and T), angiotensin II type 1 receptor (A and C) and angiotensin-converting enzyme (D and I) genes were analyzed by amplified fragment length polymorphism. A significant association was detected by chi2 analysis for angiotensinogen and angiotensin II-type I receptor allele distribution in hypertensive patients, in accordance with previous reports. Genetic data and methods are contributing more and more to epidemiological studies of complex diseases, and their application is influenced by information availability and Genome Project results.
Amplified Fragment Length Polymorphism Analysis↗
CCR5 and CCR2 gene polymorphisms in hypertensive patients.
Essential hypertension is a complex trait under polygenic control. Evidences suggests immune system involvement during pathogenesis. CC-chemokine receptor (CCR)5 and CCR2 are characterised by gene polymorphism. Variant alleles are derived from a deletion in the CCR5 gene (CCR5delta32) and a substitution mutation at the CCR2 locus (CCR264I). CCR polymorphic forms have been studied extensively as invasion cofactors for HIV-1, but they have also been implicated in immuno-related disorders. Here, we evaluate the allelic distribution of CCR5 and CCR2 genes in essential hypertension in a case-control study. Genotype frequency in a group of essential hypertensive patients (stage I-II; n=120) and a group of unrelated, healthy Caucasian subjects (n=340) is compared. CCR gene polymorphism is analysed by polymerase chain reaction and restriction enzyme digestion. A statistically significant difference was observed for CCR5 and CCR2 mutant alleles in essential hypertensive patients, compared with the controls (P=0.004 and P=0.003, respectively). CCR5delta32 and CCR264I alleles showed a 0.096 and 0.10 frequency among cases. To date, a role for the immune system in hypertension has not been clarified, nor has the predictive value of CCR polymorphisms.
Alleles↗
AGT and AT1R gene polymorphism in hypertensive heart disease.
Left ventricular hypertrophy in patients with hypertension is a main clinical prognostic entity The aim of this study was to evaluate the association between mutations at genes of the renin-angiotensin system (RAS) and the development of left ventricular hypertrophy. Genetic polymorphism in angiotensinogen (AGT) and angiotensin Il-type 1 receptor (AT1R) genes was examined in a group of well-selected essential hypertensive caucasians with left ventricular involvement (n = 40) and a group of healthy unrelated caucasians (n = 150). Cardiac morphology and function were assessed by M-mode echocardiography. Molecular variants were analysed by amplified fragment length polymorphism. We observed a statistically significant difference both for AGT and AT1R genotype distribution in patients with left ventricular hypertrophy compared with controls (p<0.05). A 0.49 and 0.225 frequency was detected among cases for T and C mutant alleles at AGT and AT1R genes. Mutations in RAS genes are involved in the pathophysiology of target-organ damage in essential hypertension. Evaluation of molecular factors conferring a risk of developing heart involvement may lead to better identification of patient subgroups and more effective control of the clinical course.
Adult↗
Angiotensin-related genes involved in essential hypertension: allelic distribution in an Italian population sample.
BACKGROUND: Blood pressure is a quantitative multifactorial trait influenced by environmental and genetic determinants. Although several candidate genes have been associated with the development of essential hypertension, the mechanisms of individual susceptibility still remain unclear. Knowledge on the distribution of genetic polymorphisms in different populations is fundamental for the assessment of the predictive value of genetic variation. METHODS: We genotyped 300 healthy normotensive subjects from the Italian population for three polymorphisms, at the angiotensinogen (AGT, M and T), angiotensin II type 1 receptor (ATIR, A and C) and angiotensin-converting enzyme (ACE, D and I) genes. Polymorphisms were analyzed by polymerase chain reaction and restriction enzyme digestion. Statistical analysis was performed to verify the agreement with the Hardy-Weinberg equilibrium. RESULTS: The observed allelic distribution was in accordance with estimates reported for Caucasian populations. Variant allelic frequencies were 0.36 for the T and C alleles at the AGT andAT1R locus and 0.47 for the I allele of the ACE gene. AT1R and ACE genotype frequencies were in Hardy-Weinberg equilibrium, while there was a deviation of the AGT genotypes from those predicted by the equation. CONCLUSIONS: The studied polymorphisms are largely distributed in the Italian population sample, with a frequency of homozygous subjects for mutant alleles ranging from 9 to 22%. Epidemiology of mutations in the genes involved in blood pressure regulation provides tools to evaluate susceptibility to hypertension.
Adult↗
Troponin I serum concentration: a new marker of left ventricular hypertrophy in patients with essential hypertension.
BACKGROUND: Troponin I, a specific cardiac muscle protein, has proven to be very helpful in detecting myocardial damage in ischemic heart disease. In order to assess if this laboratory test may also characterize some hypertensive subjects with proven cardiac damage, we compared troponin I serum concentrations of a group of patients affected by systemic hypertension and left ventricular hypertrophy (LVH) with troponin I serum concentrations of hypertensive patients without LVH and with normal controls. METHODS: Of 100 hypertensive patients consecutively enrolled in the study, 27 had an increased left ventricular mass by M-mode/two-dimensional echocardiographic examination. Of these, 4 were excluded for significant Holter ST-segment modification. Troponin I was measured in the remaining 23, in 23 age- and sex-matched hypertensive patients with normal left ventricular mass and in 23 normal controls. RESULTS: Troponin I serum concentration was higher than the upper limit of the normal values (0.5 ng/mi) in 12 of the 23 hypertensives with LVH. On the contrary, all hypertensives without LVH and all normal controls had troponin I serum concentration below the upper limit of the normal values. Consequently, the mean troponin I serum value was significantly higher in the group of hypertensive patients with LVH than in the group of patients without LVH (0.88 +/- 0.93 vs 0.27 +/- 0.08 ng/ml, p = 0.002) and in normal controls (0.88 +/- 0.93 vs 0.22 +/- 0.04 ng/ml, p = 0.0001). CONCLUSIONS: Our data indicate that a significant proportion of patients affected by essential hypertension with LVH have slightly elevated troponin I serum concentrations. This test seems to identify two subgroups of hypertensive subjects with LVH, and, considering that troponin I is a marker of myocardial damage, higher serum values probably indicate a more important cardiac involvement in the setting of a hypertensive disease.
Adult↗
Combination therapy with beta-adrenergic blockade and amlodipine as second line treatment in essential hypertension.
In hypertension both beta-blockers and calcium antagonists are drugs with proved efficacy. Because only half the patients respond to a single drug, even at full dosage, a second hypotensive agent is frequently required to obtain adequate blood pressure control. The combination of a dihydropyridine calcium antagonist and a beta-blocker can be justified by their different mechanisms of action. A randomised double blind parallel group study versus placebo was performed, in order to assess the efficacy of atenolol combined with amlodipine in the treatment of stage I-II essential hypertension not controlled by atenolol alone. Twenty-four-hour arterial blood pressure monitoring showed that amlodipine added to atenolol produced a statistically significant reduction of blood pressure values compared with placebo in patients whose blood pressure was not controlled by atenolol alone. Blood pressure circadian rhythm was unchanged. The reduction of side-effects, obtained by adding a dihydropyridine derivate to a beta-blocker, confirms the effectiveness of this combination.
Adrenergic beta-Antagonists↗
Sublingual nicardipine versus nifedipine to treat hypertensive urgencies.
Hypertensive urgencies are clinical settings in which a steady therapeutic intervention is needed, but this may be safely stretched over some hours. An appropriate antihypertensive drug to use in an urgency should show a potent but gradual effect: it should reduce BP in a short time and it should be easy to modulate the antihypertensive effect, according to individual needs. Sublingual administration is the easiest way for a therapeutical intervention in an urgency. The use of nicardipine administered sublingually was tested in comparison with nifedipine, during a hypertensive urgency, in 24 hypertensive subjects. The peak effect of nifedipine occurred within 10-20 minutes after the administration, whereas that of nicardipine occurred after 45-50 minutes; nevertheless a significant decrease both in systolic and diastolic blood pressure was already observed 20 min after nicardipine administration. The hypotensive effect of nicardipine was longer lasting than that of nifedipine. Some adverse effects were observed in the group receiving nifedipine, whereas no side effects were described by patients receiving nicardipine.
Administration, Sublingual↗
[An unusual association of psoriasis with polymyositis].
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Adolescent↗
Casual versus 24-hour ambulatory blood pressure recording in the evaluation of chronic administration of sustained-release verapamil.
Although ambulatory blood pressure monitoring has been used widely for the evaluation of antihypertensive treatment, little information is available regarding the comparison between this method and casual BP measurement during drug trials. In our study, we tested the efficacy of a new formulation of verapamil, 240 mg sustained-release tablets, and compared the degree of BP reduction as detected by casual (standard mercury manometer) and by 24-hour ambulatory recording (Spacelab ICR 5300). A statistically significant fall in casual BP was observed after verapamil with respect to placebo. Moreover, 24-hour, waking and sleeping ambulatory BPs were significantly reduced by verapamil. The mean BP reduction was similar for office (20.1/16.1 +/- 4.3/3.1 mmHg) and for day-time ambulatory monitoring (13.4/10.7 +/- 4.2/1.9 1.9 mmHg), but no correlation was found between BP fall recorded by the two techniques for individual subjects. This study suggests that sustained-release verapamil is an effective antihypertensive drug. Individual mean BP reduction outside the clinic may not be predicted from office readings and therefore ambulatory BP recording seems to provide a better basis for testing the efficacy of drugs.
Adult↗
Microalbuminuria as a marker of cardiac damage in essential hypertension.
A subclinical elevation in urinary albumin excretion (UAE) microalbuminuria is frequently seen in essential hypertension. The level of blood pressure appears to be an important factor in the development of microalbuminuria. Moreover there is some evidence to indicate that microalbuminuria may be an early marker of increased cardiovascular risk. Aim of this study was to evaluate the prevalence of UAE in hypertensives with normal left ventricular mass and to study any association with blood pressure level and with possible modification in left ventricular function. A group of 112 subjects diagnosed as having stage 1-2 essential hypertension were included in the study. Patients underwent urinary collection to evaluate UAE and to 24/hours arterial blood pressure monitoring. Moreover a complete echocardiography was performed. According with UAE levels patients were divided into three groups: A: UAE 0-15 mg/24 h, B: UAE 16-29 mg/24 h, C: UAE 30-300 mg/24 h. We found a significant correlation between 24/h SBP, 24/h DBP and UAE. We observed a significant correlation between impaired diastolic function and UAE. UAE is influenced by BP levels with better correlation with 24/h systolic values. UAE is associated with subclinical decrease of left ventricular function and may be an early marker of cardiac involvement.
Adult↗