Association of alpha1a-adrenergic receptor polymorphism and blood pressure phenotypes in the Brazilian population

Background: The alpha1A-adrenergic receptor (alpha(1A)-AR) regulates the cardiac and peripheral vascular system through sympathetic activation. Due to its important role in the regulation of vascular tone and blood pressure, we aimed to investigate the association between the Arg347Cys polymorphism in the alpha(1A)-AR gene and blood pressure phenotypes, in a large sample of Brazilians from an urban population. Methods: A total of 1568 individuals were randomly selected from the general population of the Vitoria City metropolitan area. Genetic analysis of the Arg347Cys polymorphism was conducted by polymerase chain reaction/restriction fragment length polymorphism. We have compared cardiovascular risk variables and genotypes using ANOVA, and Chi-square test for univariate comparisons and logistic regression for multivariate comparisons. Results: Association analysis indicated a significant difference between genotype groups with respect to diastolic blood pressure (p = 0.04), but not systolic blood pressure (p = 0.12). In addition, presence of the Cys/Cys genotype was marginally associated with hypertension in our population (p = 0.06). Significant interaction effects were observed between the studied genetic variant, age and physical activity. Presence of the Cys/Cys genotype was associated with hypertension only in individuals with regular physical activity (odds ratio = 1.86; p = 0.03) or younger than 45 years (odds ratio = 1.27; p = 0.04). Conclusion: Physical activity and age may potentially play a role by disclosing the effects of the Cys allele on blood pressure. According to our data it is possible that the Arg347Cys polymorphism can be used as a biomarker to disease risk in a selected group of individuals.FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)[2001/03454-5

Prostate-specific antigen as an estimator of prostate volume in the management of patients with symptomatic benign prostatic hyperplasia

Objectives: To assess the ability of serum prostate specific antigen (PSA) to estimate prostate volume (PV) to aid in the management of patients with benign prostatic hyperplasia (BPH). Methods: From 1989 to 2002, data were collected from 2264 patients complaining of lower urinary tract symptoms (LUTS) who visited the Department of Urology of the University Medical Centre Nijmegen, The Netherlands. Baseline PV and serum PSA was determined using standard techniques. All patients who had a baseline PV less than or equal to200 ml, as well as a baseline serum PSA 0-10 ng/ml, were included. Patients with a history of prostate surgery, prostate cancer and conditions other than BPH at baseline were excluded. A log-transformed linear regression model was used to estimate PV. Receiver-operating characteristic (ROC) curves were constructed to evaluate the ability of serum PSA to estimate threshold PVs in men with BPH, and to select the optimal serum PSA cut-off values. Results: The analyses included 1859 patients with a mean age of 63.5 years, mean baseline PV 43.9 ml, and mean baseline PSA value 3.1 ng/ml. PV as well as serum PSA increases with age. Linear regression analyses showed that PV and serum PSA have an age-dependent log-linear relationship, where 42% of the variance of PV can be explained by PSA and age. ROC's area under the curves (AUC) reveal that PSA has a good predictive value for assessing 'prostate enlargement', with AUC around 82% in the overall age groups irrespective of the PV cut-off values. Optimal serum PSA cut-off values for the overall study population irrespective of age are 2.0 ng/ml to detect PV >30 ml and 2.5 ng/ml to detect PV >40 ml. Conclusions: This study suggests that serum PSA can estimate prostate enlargement sufficiently accurately to be useful for therapeutic, especially medical, management. It is well accepted that the outcome of pharmacotherapy for BPH depends on baseline PV. Therefore, in the absence of reliable direct measurement of PV, serum PSA determination may be used to optimise patient management. (C) 2003 Elsevier B.V. All rights reserved