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Obesity is one of the most common disorders and a serious world wide health problem because of its association with other pathologies. The attendance rate of obesity has increased in the last century, particularly in the last decades, having already been considered by WHO as the XXI century epidemic. Overweight/Obesity is the result of the interaction between genetic and environmental factors. Only a small number of cases is due to other causes (endocrine pathologies, tumors and others). The genetic component that contributes to obesity is multifactorial, involving several genes and polymorphisms. Overweight/Obesity is a chronic condition associated with an increased risk of hypertension,type II diabetes, cardiovascular disease and various types of cancers. Genetics has been anextremely useful tool to understanding this disease. There are several important genes onthe development of overweight/obesity that are described in several association studies that establish a relationship between phenotype / genotype. Nowadays, the diagnosis of obesity is made by anthropometric factors such as, body massindex (BMI) and waist circumference, not taking into account genetic and endocrine factors leading to the pathology development, especially in individuals with family history. DNA and/or RNA molecular detection could help in the characterization of genetic changes (mutations/polymorphisms) involved in this pathology. STAB VIDA is one of the pioneers in this area, having already contributed to thedevelopment of new technologies through a kit to obesity predisposition and relateddiseases by DNA direct sequencing method.
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Methods and results 285 patients with CAD divided into three age-matched groups: group 1 (G1, n = 95), ACS and one-vessel disease (1-VD); group 2 (G2, n = 95), ACS and 2,3-VD; group 3 (G3, n = 95), chronic CS. Control group (C, n = 95) was composed of patients with suspected CAD who were found to have entirely normal coronary arteries by angiography. Gensini's score used to assess extent of CAD. ED as any value < 26 according to the International Index of Erectile Function (IIEF). ED prevalence was lower in G1 vs. G3 (22 vs. 65%, P < .0001) as a result of less atherosclerotic burden as expressed by Gensini's score [2 (0-6) vs. 40 (19-68), P = 0.0001]. Controls had ED rate values similar to G1 (24%). Group 2 ED rate, IIEF, and Gensini's scores were significantly different from G1 [55%, P < 0.0001; 24 (17-29), P = 0.0001; 21 (12.5-32), P < 0.0001] and similar to G3 suggesting that despite similar clinical presentation, ED in ACS differs according to the extent of CAD. No significant difference between groups was found in the number and type of conventional risk factors. Treatment with beta-blockers was more frequent in G3 vs. G1 and G2. In G3 patients who had ED, onset of sexual dysfunction occurred before CAD onset in 93%, with a mean time interval of 24 [12-36] months. In logistic regression analysis, age (OR=1.1; 95% confidence interval (CI), 1.05-1.16; P = < 0.0001), multi-vessel vs. single-vessel (OR=2.53; 95% CI, 1.43-4.51; P = 0.0002), and CCS vs. ACS (OR=2.32; 95% CI, 1.22-4.41; P = 0.01) were independent predictors of ED.
Several key problems still need to be addressed. For instance, it would be of great benefit to determine the structure of several PDE holoenzymes to fully understand their mechanisms of regulation. Therefore, substantial effort is being expended in this area. A concept gaining great support is the idea that different PDEs subserve different pools of cAMP and cGMP in the cell. We are only just beginning to be able to measure PDE activity in subcellular compartments of the cell in real time. This is an area that clearly needs to be developed, including identification of molecular mechanisms that provide and control PDE subcellular localization. We also need to identify good animal models that accurately reflect the regulation and roles of PDEs in human tissues as many examples now are available for different modes of regulation between mice and men. At a minimum, putative regulatory schemes identified from studies in mouse, Drosophila, or zebrafish need to be tested quickly in human tissues.
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