Browsing by Author "Barbosa, Ana Paula"
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- May the polymorphisms of iron metabolism modulate metabolic and bone remodelling parameters associated with osteoporosis?Publication . Ferreira, Joana; Silva, Bruno; Faustino, Paula; Monteiro, Cristina; Barbosa, Ana Paula; Batista, Fátima; Laires, Maria José; Bicho, Manuel; Mascarenhas, Mário RuiIntroduction:- Osteoporosis is a multifactorial disease whose interaction between genetic and environmental factors lead to a reduction of bone mineral density accompanied by changes in bone microarchitecture level, leading to a significant decrease in bone strength and an increased fracture risk. - Iron is known to play a relevant role in the development of osteoporosis as it suppresses osteoblast formation and may also stimulate osteoclast resorption of bone. As so, polymorphisms in genes affecting iron homeostasis can increase the susceptibility for the development of osteoporosis. - HFE is a major histocompatibility complex class I-like protein which gene is commonly mutated in Hereditary Hemochromatosis, a disorder characterized by excessive intestinal iron absorption and its deposition in several organs. It has been postulated that HFE may contribute to iron metabolism regulation by activating hepcidin synthesis in hepatocytes and regulating the expression of iron metabolism-related genes (ferroportin) in duodenum and other cells. - The locus encoding HFE is located on the long arm of chromosome 6 (6q22.2) and contains 2 major polymorphisms. A 845G-A transition resulting in a cys282-to-tyr (C282Y) substitution and a C-to-G transversion in exon 2 resulting in a his63-to-asp substitution (H63D). - Haptoglobin (Hp) is an acute phase protein that binds free hemoglobin (Hb) released from erythrocytes with high affinity and thereby inhibits its oxidative activity. - The locus encoding haptoglobin is located on the long arm of chromosome 16 (16q22.2) and presents a copy number variation polymorphism (CNV) that results from an internal duplication of a gene segment (exons 3 and 4). This gives rise to three different genotypes (Hp1.1, Hp 2.1 and Hp2.2) that modulate the half-life of Hp-Hb complex, its plasma concentration as well as other functions (angiogenesis, immune, etc)
- Osteoporosis after menopause: interaction between genes related to iron metabolism and estradiolPublication . Aguiar, Laura; Ferreira, Joana; Binda Pereira, Raquel; Barbosa, Ana Paula; Mascarenhas, Mário Rui; Faustino, Paula; Inácio, Ângela; Bicho, ManuelIntroduction: Osteoporosis is a common metabolic bone disease characterized by reduced bone mass and increased risk of fragility fractures. The pathogenesis of this disease is complex and influenced by multiple risk factors, where genetic factors play an important role. Menopause predisposes women to osteoporosis due to declining estrogen levels. Osteoporosis and iron metabolism have an important relationship. Iron overload suppresses osteoblast formation and stimulate osteoclast resorption of bone, suggesting that polymorphisms in genes affecting iron homeostasis can increase the susceptibility for the development of osteoporosis. Objectives: This study aimed to investigate the potential implication of genetic polymorphisms in genes related to iron metabolism and their interaction with estradiol in the development of osteoporosis in a sample of postmenopausal women. Material and methods: A case-control study was carried out for a sample of 169 Portuguese postmenopausal women, of which 78 had osteoporosis and 91 had normal bone mass. Polymorphic analyzes on the HFE gene (H63D and C282Y) were performed by PCR-RFLP. The haptoglobin (Hp) phenotype was determined by polyacrylamide gel electrophoresis. Plasma 17b-estradiol concentration was determined by ELISA. All statistical analyzes were performed using SPSS software, version 24.0. Results; An association was found between lower levels of 17b-estradiol and osteoporosis [OR (95% CI) Z 5,946 (2,199-16,079); P!0.001]. When the genes were analyzed separately, no significant differences were found between the two populations in relation to the polymorphisms under study. However, women with the presence of the H allele of the H63D polymorphism of the HFE gene and lower levels of estradiol had an increased risk of developing osteoporosis [OR (95% CI) Z 22,750 (2,492-207,731); PZ0.001], as well as the presence of the CC genotype of the C282Y polymorphism of the HFE gene and lower levels of estradiol [OR (95% CI) Z 11,667 (2,139-63,638); PZ0.002]. Also women who had the Hp 2 allele and lower levels of estradiol had an increased risk of developing osteoporosis [OR (95% CI) Z 7,023 (1,813-27,200); PZ0.005]. Conclusion: Since these genes are related to iron metabolism, the results of this study suggest an action of this metabolism in interaction with estradiol levels in the development of osteoporosis in postmenopausal women.
- Polimorfismos genéticos e a sua interação na suscetibilidade para a hipertensão na população portuguesaPublication . Aguiar, Laura; Semente, Ildegário; Ferreira, Joana; Mascarenhas, Mário Rui; Barbosa, Ana Paula; Menezes Falcão, Luís; Faustino, Paula; Bicho, Manuel; Inácio, ÂngelaIntrodução: A Hipertensão Arterial (HTA) é um fator de risco cardiovascular muito prevalente em Portugal. Esta patologia é multifatorial, envolvendo fatores genéticos e ambientais. Objetivo: Este estudo teve como objetivo investigar a potencial implicação de polimorfismos genéticos nos genes da sintase do óxido nítrico endotelial (eNOS) e da enzima conversora da angiotensina (ECA) e da sua interação no desenvolvimento da HTA na população portuguesa. Material e métodos: Foi realizado um estudo de caso-controlo para uma amostra de 377 indivíduos portugueses, dos quais 243 hipertensos (90 hipertensos ligeiros e 153 hipertensos graves) e 134 normotensos. As amostras foram recolhidas no Centro Hospitalar Lisboa Norte, no Hospital de Santa Maria. As análises polimórficas do número variável de repetições em tandem (VNTR) no intrão 4 (repetição em tandem de 27 pb) do gene eNOS e do polimorfismo ECA I/D (inserção/ deleção) foram realizadas por reação em cadeia da polimerase (PCR). Todas as análises estatísticas foram realizadas recorrendo ao software SPSS, versão 24.0, sendo o nível de significância estatística estabelecido para p <0,05. Resultados: Quando os polimorfismos foram analisados isoladamente, encontrou-se uma associação entre alelo 4a (quatro cópias de repetições de 27 pb) do gene eNOS e a hipertensão, em especial a hipertensão grave (p =0,001). Em relação ao gene ECA, não se encontram diferenças estatisticamente significativas entre doentes e controlos. No entanto, para a interação entre os polimorfismos nos genes eNOS e ECA, encontrou-se uma associação do alelo 4a do gene eNOS e do alelo D do gene ECA e a hipertensão ligeira (p =0,049). Conclusão: Os nossos resultados mostram uma associação entre o gene eNOS e a HTA na população portuguesa. Os resultados ainda sugerem uma relação entre a interação epistática nos genes eNOS e ECA e a suscetibilidade para o desenvolvimento de hipertensão. A identificação de polimorfismos genéticos que possam influenciar o desenvolvimento e gravidade da HTA, bem como as suas interações epistáticas, pode permitir um diagnóstico mais precoce e específico, que pode proporcionar melhores estratégias terapêuticas e de prevenção, para esta doença tão prevalente em Portugal.
- A WNK4 gene variant relates to osteoporosis and not to hypertension in the Portuguese populationPublication . Mendes, Ana Isabel; Mascarenhas, Mário Rui; Matos, Sónia; Sousa, Inês; Ferreira, Joana; Barbosa, Ana Paula; Bicho, Manuel; Jordan, PeterGermline mutations in the WNK4 gene originate Gordon syndrome or pseudohypoaldosteronism type II, a familial form of hypertension with hyperkalemia and hypercalciuria. In order to elucidate the contribution of WNK4 genetic variants to hypertension and/or osteoporosis, we analyzed 271 control individuals and a cohort of 448 hypertensive and 372 osteoporosis patients from the Portuguese population. Ten genetic variants were detected in 4.3% of the population under study, none of which revealed any significant association to the hypertension phenotype. In contrast, a rare missense alteration within exon 17 in a highly conserved arginine residue showed a possible tendency for association to the osteoporosis group. Our data suggest that WNK4 polymorphism rs56116165 is a rare allelic variant in a candidate gene with a biological function in renal calcium homeostasis that may contribute to a genetic predisposition to osteoporosis.