Effetto del genotipo sulla massa ventricolare sinistra e sugli eventi cardiovascolari nell'ipertensione arteriosa

Background. Left ventricular mass (LVM) is increased in 20-25% of untreated hypertensive patients and influences cardiovascular morbidity and mortality. It is kept under control by mineralocorticoids, angiotensin II, genetic and emodynamics factors. Association of the renin angiotensin aldosterone system (RAA) genes and sodium sensitivity with LVM has been reported by many authors but it remains controversial for the small sample size of the cohorts studied and for the study design (methodology and stratification, genetic heterogeneity). Aim of the study. To assess the cardiovascular events as a function of genotype (RAA system genes and sodium sensitivity) and of LVM on a large cohort of untreated, genetically homogeneus esssential hypertensive patients. We studied on 473 patients Methods. n=473 untreated, genetically homogeneous essential hypertensive patients were studied (age: 47.3 ± 9.8 old); M/F: 257/172; BP at the time of first visit: 156 mmHg ). All patients’ data were recorded on electronic file. Results. The A1166C polymorphism of the AT1R gene was found associated with LVM. No association between the genes under study and cardiovascular events was found even when they were analysed as a function of cardiac mass. Conclusions. our data confirm that LVM is a determinant of cardiovascular damage and indicate that association studies do not have the potential to reveal the genetic component of cardiovascular events

Association of <i>ATP1A1</i> and <i>Dear</i> Single-Nucleotide Polymorphism Haplotypes With Essential Hypertension

Essential hypertension remains a major risk factor for cardiovascular and cerebrovascular diseases. As a complex multifactorial disease, elucidation of susceptibility loci remains elusive. ATP1A1 and Dear are candidate genes for 2 closely linked rat chromosome-2 blood pressure quantitative trait loci. Because corresponding human syntenic regions are on different chromosomes, investigation of ATP1A1 (chromosome [chr]-1p21) and Dear (chr-4q31.3) facilitates genetic analyses of each blood pressure quantitative trait locus in human hypertension. Here we report the association of human ATP1A1 ( P <0.000005) and Dear ( P <0.03) with hypertension in a relatively isolated, case/control hypertension cohort from northern Sardinia by single-nucleotide polymorphism haplotype analysis. Sex-specific haplotype analyses detected stronger association of both loci with hypertension in males than in females. Haplotype trend-regression analyses support ATP1A1 and Dear as independent susceptibility loci and reveal haplotype-specific association with hypertension and normotension, thus delineating haplotype-specific subsets of hypertension. Although investigation in other cohorts needs to be performed to determine genetic effects in other populations, haplotype subtyping already allows systematic stratification of susceptibility and, hence, clinical heterogeneity, a prerequisite for unraveling the polygenic etiology and polygene–environment interactions in essential hypertension. As hypertension susceptibility genes, coexpression of ATP1A1 and Dear in both renal tubular cells and vascular endothelium suggest a cellular pathogenic scaffold for polygenic mechanisms of hypertension, as well as the hypothesis that ATP1A1 and/or Dear could contribute to the known renal and vascular endothelial dysfunction associated with essential (polygenic) hypertension

Prevalence and clinical features of heterozygous carriers of autosomal recessive hypercholesterolemia in Sardinia

Objective: Autosomal recessive hypercholesterolemia (ARH) is a lipid disorder caused by mutations in a specific adaptor protein for the LDL receptor. ARH is rare except in Sardinia where three alleles (ARH1, ARH2 and ARH3) explain most of cases. The prevalence of ARH heterozygotes in Sardinia is not well determined as well as inconclusive data are available on the effect of the ARH carrier status on LDL cholesterol (LDL-C) and coronary risk. Methods: 3410 Sardinians (986 blood donors, 1709 with hypertension and 715 with myocardial infarction (MI)) were screened for ARH alleles. For comparison purposes, lipid data of 60 ARH heterozygous carriers and 60 non-carriers identified within 24 ARH families were also considered. Results: In the whole study cohort, no ARH homozygotes were found, but 15 ARH1 (0.44%) and 9 ARH2 (0.26%) heterozygous carriers were identified. The frequency of ARH alleles in blood donors was 0.0030, not different from that in hypertensive subjects (0.0032). ARH alleles tended to be more common in MI patients (0.0049), but no association between ARH carrier status and MI risk was detected after controlling for conventional risk factors. ARH carriers and non-carriers showed similar LDL-C levels. This result was confirmed when ARH carriers and non-carriers identified throughout family-based and population-based screenings were combined and compared (141.0 +/- 41 mg/dl vs. 137.0 +/- 41 mg/dl, respectively; p = 0.19). Conclusions: These data indicate that the frequency of ARH heterozygotes in Sardinia is similar to 1:143 individuals, thus making this condition one of the most common in the Sardinian population. However, ARH carrier status does not influence LDL-C concentration and coronary risk, thus suggesting that ARH can be regarded as a truly recessive disorder. (C) 2009 Elsevier Ireland Ltd. All rights reserved

Genome-wide association study identifies CAMKID variants involved in blood pressure response to losartan: the SOPHIA study

BACKGROUND: Essential hypertension arises from the combined effect of genetic and environmental factors. A pharmacogenomics approach could help to identify additional molecular mechanisms involved in its pathogenesis. AIM: The aim of SOPHIA study was to identify genetic polymorphisms regulating blood pressure response to the angiotensin II receptor blocker, losartan, with a whole-genome approach. MATERIALS & METHODS: We performed a genome-wide association study on blood pressure response in 372 hypertensives treated with losartan and we looked for replication in two independent samples. RESULTS: We identified a peak of association in CAMK1D gene (rs10752271, effect size -5.5 \ub1 0.94 mmHg, p = 1.2 7 10(-8)). CAMK1D encodes a protein that belongs to the regulatory pathway involved in aldosterone synthesis. We tested the specificity of rs10752271 for losartan in hypertensives treated with hydrochlorothiazide and we validated it in silico in the GENRES cohort. CONCLUSION: Using a genome-wide approach, we identified the CAMK1D gene as a novel locus associated with blood pressure response to losartan. CAMK1D gene characterization may represent a useful tool to personalize the treatment of essential hypertension

Factors Enhancing Treatment of Hepatitis C Virus-Infected Italian People Who Use Drugs: The CLEO-GRECAS Experience

We assessed the performance of direct-acting antivirals (DAAs) in hepatitis C virus (HCV)-infected people who use drugs (PWUDs) in terms of sustained virological response (SVR) and adherence rates in comparison to a location-matched cohort of non-PWUD HCV patients