Browsing by Author "Boleixa, D."
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- Association between vitamin D receptor (VDR) gene polymorphisms and systemic lupus erythematosus in Portuguese patientsPublication . Carvalho, C.; Marinho, A.; Leal, B.; Bettencourt, A.; Boleixa, D.; Almeida, I.; Farinha, F.; Costa, P.P.; Vasconcelos, C.; Silva, B.M.Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown origin, in which both genetic and environmental factors are involved. One such environmental factor is vitamin D, a vital hormone that plays a specific function in the immune system homeostasis, acting through a nuclear receptor (VDR) expressed in all immune cells. Several polymorphisms of the gene that encodes this receptor have been described. Though inconsistently, these polymorphisms have been associated with clinical manifestations and SLE development.The aim of this study was to determine the possible association between VDR gene polymorphisms (BsmI, ApaI, TaqI e FokI) and SLE susceptibility and severity, in a cohort of lupus patients from the north of Portugal.A total of 170 patients (F = 155, M = 15; age = 45 ± 13.4 years) with SLE (diagnosed according the American College of Rheumatology criteria) with at least five years of disease evolution and followed in the Autoimmune Disease Clinical Immunology Unit of Centro Hospitalar do Porto were studied. Patients and 192 ethnicity-matched controls were genotyped for BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236) and FokI (rs2228570) polymorphisms by TaqMan allelic discrimination assay. Disease severity was assessed by SLICC damage score, number of affected organs, number of severe flares and pharmacological history.SLE patients with the CT genotype of FokI polymorphism have a higher SLICC value (p = 0.031). The same result was observed for the group of patients with the TT genotype of TaqI polymorphism (p = 0.046). No differences were observed in VDR genotype between patients and controls. Also, we observed that the other clinical features analysed were not influenced by VDR polymorphisms.Our study confirms a possible role of VDR gene polymorphisms in SLE. A positive association was found between VDR polymorphisms and SLE severity (chronic damage). The presence of CT genotype of FokI and TT genotype of TaqI seems to confer a worse prognosis and may constitute a risk factor for higher long-term cumulative damage in SLE patients.
- Circulating microRNAs as potential biomarkers for genetic generalized epilepsies: a three microRNA panelPublication . Martins‐Ferreira, R.; Chaves, J.; Carvalho, C.; Bettencourt, A.; Chorão, R.; Freitas, J.; Samões, R.; Boleixa, D.; Lopes, J.; Ramalheira, J.; Silva, B.M.; Martins da Silva, A.; Costa, P. P.; Leal, B.Background and purpose: Genetic generalized epilepsies (GGEs) encompass a group of syndromes of mainly genetic causes, characterized by the involvement of both hemispheres. MicroRNAs (miRNAs) are small non-coding RNAs with a critical role in the regulation of neuronal biological processes through gene expression modulation. Dysregulated miRNA expression has been shown in epilepsy. Due to their stability in biological fluids like serum, miRNAs have assumed a prominent role in biomarker research. Our aim was to evaluate circulating levels of three miRNAs in GGE patients and assess their putative diagnostic value. Methods: MiR-146a, miR-155 and miR-132 were quantified by real-time polymerase chain reaction in the serum of 79 GGE patients (47 women, 32 men, 35.1 ± 12.4 years) and 67 healthy individuals (41 women, 26 men, 42.4 ± 10.1 years). Relative expression values were calculated using the 2-ΔΔCt method. Receiver operating characteristic curve analysis was performed to assess diagnostic value. MiRNA expression was correlated with clinicopathological features. Results: Serum levels of miR-146a and miR-155 were significantly upregulated in GGE patients relative to controls (3.13 and 6.05, respectively). Combined miR-146a, miR-155 and miR-132 serum levels performed well as a diagnostic biomarker, discriminating GGE patients from controls with an area under the curve of 0.85, 80% specificity and 73% sensitivity. Conclusions: Our results indicate that miR-146a, miR-155 and miR-132 may partake in GGE epileptogenesis. A panel of three circulating miRNAs with potential value as a GGE biomarker is reported for the first time. Novel biomarkers may help to identify new treatment targets and contribute to improved patients' quality of life through earlier diagnosis and a more precise prognosis.
- Mesial temporal lobe epilepsy and serotonin: the role of HTR2A receptorPublication . Chaves, J.; Leal, B.; Carvalho, C.; Bettencourt, A.; Bras, S.; Barreira, A.; Boleixa, D.; Martins da Silva, A.; Costa, P.P.; Martins da Silva, B.Purpose: Evidences from animal models have demonstrated that depletion of brain serotonin (5-HT), a neurotransmitter with a pivotal role in neurodevelopment and brain plasticity, lowers the threshold to induced seizures. It was also demonstrated that anti-epileptic drugs increase endogenous 5-HT concentrations. Studies in brain tissue from Mesial Temporal lobe Epilepsy (MTLE) patients have showed that serotonin type 2a receptor (HTR2A) is downregulated in these patients. HTR2A expression levels may be modulated by a 102 T>C polymorphism. The aim of this study was to analyse the association between 102T>C polymorphism and the development and clinical features of MTLE-HS in a Portuguese population. Methods: A cohort of 112 MTLE-HS patients (62F, 50M, mean age = 44 11 years, age of onset = 13 9 years, 97 patients with drug refractory epilepsy) was compared with a cohort of 183 healthy individuals (HI). Genotyping was performed by Real Time PCR using High Melting Resolution methodology. Results: HTR2A 102 T>C genotype frequencies were similar between patients and controls (TT: 24.1% vs. 25.1% in HI; TC: 45.5% vs. 43.2% in HI; CC: 31.3% vs. 31.7% in HI). No association was found between this polymorphism and MTLE-HS clinical features (age of onset, FS antecedents and anti-epileptic drug response). Conclusion: The present results do not provide evidence that HTR2A polymorphism 102T>C may confer susceptibility to MTLE-HS. Nevertheless a possible role for the serotonergic system in epileptogenesis cannot be excluded. The study of other 5-HT receptors and transporters is underway.