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Polimorfismos genéticos relacionados com o metabolismo do sódio e a susceptibilidade para a perda de massa óssea
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Resumo(s)
A osteoporose é uma doença sistêmica progressiva, caracterizada pela redução da densidade mineral óssea (DMO), pela deterioração da microarquitetura do osso, com consequente aumento da fragilidade óssea e da suscetibilidade a fraturas. Os objetivos deste estudo foram: determinar se polimorfismos genéticos de genes envolvidos no metabolismo do sódio (AGT, ECA, AGTR1 e SCNN1G) poderiam estar associados a alterações da DMO e ao risco de fratura (RF); estudar a relação de parâmetros metabólicos de interesse (adiponectina, sódio, PCRus, dentre outros) com as alterações da DMO, com o RF e com os polimorfismos genéticos. O estudo incluiu 254 indivíduos divididos em 3 grupos: DMO normal (N=85), DMO reduzida (N=86) e Osteoporose (N=83). Os principais resultados foram: Apesar de os polimorfismos genéticos dos genes estudados não terem apresentado associação direta com as alterações da DMO, estiveram associados com o RF e com alterações bioquímicas de suscetibilidade à osteoporose. O alelo T do polimorfismo do AGT esteve associado ao aumento da PCRus e do risco de fratura no grupo DMO reduzida. O alelo D do polimorfismo da ECA esteve associado ao aumento da adiponectina no grupo Osteoporose. O alelo C do polimorfismo do AGTR1 esteve associado ao aumento do sódio e da PCRus no grupo Osteoporose. Relativamente à bioquímica, o grupo Osteoporose apresentou: aumento da adiponectina, redução da PCRus e melhor sensibilidade à insulina. Adicionalmente, o RF se mostrou aumentado no grupo Osteoporose, independentemente do uso de bisfosfonatos. Apesar de este ser um campo de investigação pouco explorado, os resultados deste trabalho apontam para um possível papel deletério da adiponectina no metabolismo ósseo, aumentando assim o conhecimento sobre a fisiopatologia e a possibilidade de novas medidas preventivas e terapêuticas para a perda de massa óssea.
Osteoporosis is a progressive systemic disease characterized by bone mineral density (BMD), reduction, deterioration of bone microarchitecture, and a consequent increase in bone fragility and susceptibility to fractures. The objectives of this study were: to determine whether genetic polymorphisms of genes involved in sodium metabolism (AGT, ECA, AGTR1 e SCNN1G) could be associated with changes in bone mass and in fracture risk; to study the relationship of metabolic parameters of interest (adiponectin, sodium, PCRus, among others) with changes in bone mass, in fracture risk and with genetic polymorphisms. The present study included 254 individuals divided into 3 groups: Normal BMD (N=85), Reduced BMD (N=86) and Osteoporosis (N=83). The main results were: although genetic polymorphisms studied were not directly associated with alterations of bone mass, they were associated with fracture risk and with biochemical changes related to osteoporosis susceptibility. The T allele of the AGT polymorphism was associated with increased PCRus and fracture risk in the DMO-R group. The D allele of the ECA polymorphism was associated with increased adiponectin in the Osteoporosis group. The C allele of the SCNN1G polymorphism was associated with increased sodium and PCRus in the Osteoporosis group. Regarding biochemistry, the Osteoporosis group presented: an increased level of adiponectin, a reduced level of PCRus and an improved insulin sensitivity. Additionally, the fracture risk was high in the Osteoporosis group, regardless of the use of bisphosphonates. Although this is an underexplored field of investigation, the results of this work point to a possible deleterious role of adiponectin in bone metabolism, thus increasing the knowledge about the pathophysiology and the possibility of developing new preventive and therapeutic measures for the bone mass loss.
Osteoporosis is a progressive systemic disease characterized by bone mineral density (BMD), reduction, deterioration of bone microarchitecture, and a consequent increase in bone fragility and susceptibility to fractures. The objectives of this study were: to determine whether genetic polymorphisms of genes involved in sodium metabolism (AGT, ECA, AGTR1 e SCNN1G) could be associated with changes in bone mass and in fracture risk; to study the relationship of metabolic parameters of interest (adiponectin, sodium, PCRus, among others) with changes in bone mass, in fracture risk and with genetic polymorphisms. The present study included 254 individuals divided into 3 groups: Normal BMD (N=85), Reduced BMD (N=86) and Osteoporosis (N=83). The main results were: although genetic polymorphisms studied were not directly associated with alterations of bone mass, they were associated with fracture risk and with biochemical changes related to osteoporosis susceptibility. The T allele of the AGT polymorphism was associated with increased PCRus and fracture risk in the DMO-R group. The D allele of the ECA polymorphism was associated with increased adiponectin in the Osteoporosis group. The C allele of the SCNN1G polymorphism was associated with increased sodium and PCRus in the Osteoporosis group. Regarding biochemistry, the Osteoporosis group presented: an increased level of adiponectin, a reduced level of PCRus and an improved insulin sensitivity. Additionally, the fracture risk was high in the Osteoporosis group, regardless of the use of bisphosphonates. Although this is an underexplored field of investigation, the results of this work point to a possible deleterious role of adiponectin in bone metabolism, thus increasing the knowledge about the pathophysiology and the possibility of developing new preventive and therapeutic measures for the bone mass loss.
Descrição
Tese de mestrado, Doenças Metabólicas e do Comportamento Alimentar, Universidade de Lisboa, Faculdade de Medicina, 2022
Palavras-chave
Adiponectina Excesso ponderal Obesidade Osteoporose Risco de fratura Teses de mestrado - 2022