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Abstract(s)
A diabetes mellitus tipo 1 (DM1) é uma doença autoimune que resulta da destruição selectiva das células produtoras de insulina, as células ß pancreáticas, em indivíduos geneticamente susceptíveis. A vitamina D (vit D) é a principal responsável pela manutenção dos níveis de cálcio e fosfato e pelo metabolismo ósseo. No entanto, a vit D está também envolvida na modulação da resposta imunitária e tem sido consistentemente associada a doenças autoimunes, como a DM1. Doentes com DM1 apresentam uma maior prevalência de défice de vit D e a suplementação com vit D parece diminuir o risco para DM1, sugerindo uma associação entre a DM1 e a vit D. Os níveis de vit D dependem parcialmente da dieta e da exposição solar mas também de factores genéticos. Os polimorfismos de nucleótido único (SNP’s) localizados nas proximidades ou nos genes que codificam enzimas cruciais para a síntese (DHCR7-rs12785878), metabolismo (CYP2R1-rs2060793) e catabolismo (CYP24A1-rs6012897) da vit D, têm mostrado associação com os níveis de vit D e com o risco para a DM1. O objectivo deste estudo foi determinar a associação entre estes 3 SNP’s presentes na via de metabolismo da vit D e a susceptibilidade genética para a DM1 na população portuguesa.
Foi desenhado um estudo caso-controlo de modo a analisar a prevalência dos SNP’s em 320 doentes DM1 e 486 controlos saudáveis através das técnicas de PCR e de genotipagem por enzimas de restrição. As frequências alélicas e genotípicas foram comparadas entre doentes e controlos. Paralelamente avaliámos a associação destes polimorfismos com vários parâmetros clínicos da doença.
Os resultados sugerem que o polimorfismo CYP2R1-rs2060793 está associado com um aumento do risco de incidência da DM1. Observámos também uma possível associação entre este polimorfismo e o desenvolvimento da retinopatia diabética. Quanto ao polimorfismo DHCR7-rs12785878 verificou-se uma possível associação com a idade de diagnóstico e o genótipo heterozigótico parece estar associado com o desenvolvimento de anticorpos anti-GAD65. Detectámos ainda uma tendência de associação entre os SNP’s DHCR7-rs12785878 e CYP24A1-rs6013897 e o género do doente. As descobertas feitas necessitam de ser confirmadas e reavaliadas em novos estudos com populações mais numerosas, no entanto, podem contribuir para uma melhor compreensão da patogénese da DM1 e o papel da vit D na autoimunidade e na susceptibilidade genética para a DM1.
Type 1 Diabetes (T1D) is an autoimmune disease that results from the selective destruction of insulin producing cells, the pancreatic ß cells, in genetic susceptible individuals. Vitamin D (vit D) is the main responsible for the maintenance of calcium and phosphate levels and bone metabolism. However, vit D is also involved in the modulation of the immune response, and has been consistently associated with autoimmune diseases, including T1D. Patients with T1D have a higher prevalence of vit D deficiency and supplementation with vit D seems to reduce the risk for T1D, suggesting an association between T1D and vit D. Serum levels of vit D partly depend on diet and sunlight exposure, however, genetic factors are also involved. Single nucleotide polymorphisms (SNP’s) located within or near genes that encode crucial enzymes for the synthesis (DHCR7-rs12785878), metabolism (CYP2R1-rs2060793) and catabolism (CYP24A1-rs6012897) of vit D have been associated with serum levels of vit D and with the risk for T1D. The aim of this study was to determine the association between these three SNP’s, in the vit D pathway and the genetic susceptibility to T1D in the Portuguese population. We conducted a case-control study to analyse the prevalence of these SNP’s in 320 T1D patients and 486 healthy controls, using PCR and restriction fragments length polymorphism techniques for the genotyping of the individuals. Allele and genotype frequencies were compared between patients and controls. We also analysed the association of these polymorphisms with several clinical parameters of the disease. The results suggest that the CYP2R1-rs2060793 polymorphism is associated with an increased risk of T1D. We also observed a possible relation between this SNP and the development of diabetic retinopathy. A possible association between the DHCR7-rs12785878 polymorphism and the age of diagnosis was observed, as the heterozygote genotype seems to be associated with the development of anti-GAD65 antibodies. We detected a trend of association between the DHCR7-rs12785878 and CYP24A1-rs6013897 SNP’s and the gender of the patient. Our findings need to be confirmed and reassessed in new studies with larger populations, however, they may contribute to a better understanding of the pathogenesis of T1D and of the role of vit D in autoimmunity and in the genetic susceptibility to T1D.
Type 1 Diabetes (T1D) is an autoimmune disease that results from the selective destruction of insulin producing cells, the pancreatic ß cells, in genetic susceptible individuals. Vitamin D (vit D) is the main responsible for the maintenance of calcium and phosphate levels and bone metabolism. However, vit D is also involved in the modulation of the immune response, and has been consistently associated with autoimmune diseases, including T1D. Patients with T1D have a higher prevalence of vit D deficiency and supplementation with vit D seems to reduce the risk for T1D, suggesting an association between T1D and vit D. Serum levels of vit D partly depend on diet and sunlight exposure, however, genetic factors are also involved. Single nucleotide polymorphisms (SNP’s) located within or near genes that encode crucial enzymes for the synthesis (DHCR7-rs12785878), metabolism (CYP2R1-rs2060793) and catabolism (CYP24A1-rs6012897) of vit D have been associated with serum levels of vit D and with the risk for T1D. The aim of this study was to determine the association between these three SNP’s, in the vit D pathway and the genetic susceptibility to T1D in the Portuguese population. We conducted a case-control study to analyse the prevalence of these SNP’s in 320 T1D patients and 486 healthy controls, using PCR and restriction fragments length polymorphism techniques for the genotyping of the individuals. Allele and genotype frequencies were compared between patients and controls. We also analysed the association of these polymorphisms with several clinical parameters of the disease. The results suggest that the CYP2R1-rs2060793 polymorphism is associated with an increased risk of T1D. We also observed a possible relation between this SNP and the development of diabetic retinopathy. A possible association between the DHCR7-rs12785878 polymorphism and the age of diagnosis was observed, as the heterozygote genotype seems to be associated with the development of anti-GAD65 antibodies. We detected a trend of association between the DHCR7-rs12785878 and CYP24A1-rs6013897 SNP’s and the gender of the patient. Our findings need to be confirmed and reassessed in new studies with larger populations, however, they may contribute to a better understanding of the pathogenesis of T1D and of the role of vit D in autoimmunity and in the genetic susceptibility to T1D.
Description
Keywords
Diabetes Mellitus Tipo 1 Endocrinologia Genética Polimorfismo Vitamina D