Browsing by Author "Camacho, Ana"
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- Functional analysis of two novel TBX5 variants present in individuals with Holt-Oram syndrome with different clinical manifestationsPublication . Varela, Debora; Varela, Tatiana; Conceição, Natércia; Ferreira, Angela; Marques, Nuno; Silva, Ana Paula; Azevedo, Pedro; Pereira, Salome; Camacho, Ana; de Jesus, Ilidio; Cancela, M. LeonorHolt-Oram syndrome (HOS) is a rare disorder characterized by cardiac and upper-limb defects. Pathogenic variants in TBX5-a gene encoding a transcription factor important for heart and skeletal development-are the only known cause of HOS. Here, we present the identification and functional analysis of two novel TBX5 pathogenic variants found in two individuals with HOS presenting distinct phenotypes. The individual with the c.905delA variant has a severe cardiac phenotype but mild skeletal defects, unlike the individual with the c.246_249delGATG variant who has no cardiac problems but severe upper limbs malformations, including phocomelia. Both frameshift variants, c.246_249delGATG and c.905delA, generate mRNAs harbouring premature stop codons which, if not degraded by nonsense mediated decay, will lead to the production of shorter TBX5 proteins, p.Gln302Argfs*92 and p.Met83Phefs*6, respectively. Immunocytochemistry results suggest that both mutated proteins are produced and furthermore, like the wild-type protein, p.Gln302Argfs*92 mutant appears to be mainly localized in the nucleus, in contrast with p.Met83Phefs*6 mutant that displays a higher level of cytoplasmic localization. In addition, luciferase activity analysis revealed that none of the TBX5 mutants are capable of transactivating the NPPA promoter. In conclusion, our results provide evidence that both pathogenic variants cause a severe TBX5 loss-of-function, dramatically reducing its biological activity. The absence of cardiac problems in the individual with the p.Met83Phefs*6 variant supports the existence of other mechanisms/genes underlying the pathogenesis of HOS and/or the existence of an age-related delay in the development of a more serious cardiac phenotype. Further studies are required to understand the differential effects observed in the phenotypes of both individuals.
- Mineral metabolism and inflammation: factors related to left ventricular hypertrophy in patients with diabetic nephropathyPublication . Jerónimo, Teresa; Fragoso, Andr?; Mendes, Filipa; Silva, Ana Paula; Pimentel, Ana; Tavares, Nelson; Camacho, Ana; Neves, Pedro LeãoLeft ventricular hypertrophy (LVH) is an important risk factor for cardiovascular disease in patients with diabetic nephropathy (DN) and is an independent predictor of mortality in patients with chronic kidney disease (CKD). The aim of this study was to evaluate the association of LVH with mineral metabolism and inflammation in a population of patients with DN. In an observational study were included 119 type 2 diabetic patients with CKD stages 3 and 4. The population was divided into two groups, according to the presence of LVH: group 1 (G-1) with LVH (left ventricular mass index (LVMI) > 125 g/m2 in male patients and LVMI > 110 g/m2 in female patients) and group 2 (G-2) without LVH (LVMI ? 125 g/m2 in male patients and LVMI ? 110 g/m2 in female patients). The patient characteristics of each group were compared regarding several biological and laboratory parameters. Patients with LVH displayed lower values of estimated glomerular filtration rate (eGFR) (p = 0.0001) and albumin (p = 0.046), and higher levels of phosphorus (p = 0.0001), intact parathyroid hormone (iPTH) (p = 0.0001), insulin resistance (HOMA-IR) (p = 0.0001) and interleukin-6 (IL-6) (p = 0.0001), compared with patients without LVH. In a logistic regression model, phosphorus (odd ratio (OR) = 1.825 (1.075-4.414), p = 0.038), iPTH (OR = 1.991 (1.098-3.000), p = 0.004) and IL-6 (OR = 3.538 (1.863-6.719), p = 0.0001) were independently related to LVH. In a multiple linear regression model, phosphorus (r = 0.602, p = 0.038), iPTH (r = 1.009, p = 0.044) and IL-6 (r = 1.264, p = 0.0001) were positively related to LVMI. Phosphorus, PTH and IL-6 were related to LVH in our diabetic population with CKD stages 3 and 4
- What is the role of apelin regarding cardiovascular risk and progression of renal disease in type 2 diabetic patients with diabetic nephropathy?Publication . Silva, Ana Paula; Fragoso, Andre; Silva, Claudia; Viegas, Carla; Tavares, Nelson; Guilherme, Patricia; Santos, Nelio; Rato, Fatima; Camacho, Ana; Cavaco, Cidalia; Pereira, Victor; Faisca, Marilia; Ataide, Joao; Jesus, Ilidio; Neves, Pedro LeãoAims. To evaluate the association of different apelin levels with cardiovascular mortality, hospitalization, renal function, and cardiovascular risk factors in type 2 diabetic patients with mild to moderate CKD. Methods. An observational, prospective study involving 150 patients divided into groups according to baseline apelin levels: 1 <= 98pg/mL, 2 = 98-328 pg/mL, and 3 >= 329 pg/mL. Baseline characteristics were analyzed and compared. Multivariate Cox regression was used to find out predictors of cardiovascular mortality, and multivariate logistic regression was used to find out predictors of hospitalization and disease progression. Simple linear regressions and Pearson correlations were used to investigate correlations between apelin and renal disease and cardiovascular risk factors. Results. Patients' survival at 83 months in groups 1, 2, and 3 was 39%, 40%, and 71.2%, respectively (P = 0.046). Apelin, age, and eGFR were independent predictors of mortality, and apelin, creatinine, eGFR, resistin, and visfatin were independent predictors of hospitalization. Apelin levels were negatively correlated with cardiovascular risk factors and positively correlated with eGFR. Patients with lower apelin levels were more likely to start a depurative technique. Conclusions. Apelin levels might have a significant clinical use as a marker/predictor of cardiovascular mortality and hospitalization or even as a therapeutic agent for CKD patients with cardiovascular disease.