RESUMO
Growing data supported that epigenetic modifications, including altered DNA methylation have a potential role in the pathogenesis of autoimmune thyroid diseases (AITD). In the present study we aimed to investigate the methylation status of ICAM-1 gene promoter in patients with AITD. Forty patients with Graves' disease (GD), 40 patients with Hashimoto thyroiditis (HT) and 40 normal controls were included. DNA extraction from blood samples was done to analyze the ICAM-1 methylation status using methylation-specific PCR method. RNA was also extracted to determine the ICAM-1 expression values by real time PCR. We found that the differences in the frequency of ICAM-1 methylation status between GD or HT and healthy individuals were statistically significant (p = 0.04, 0.018 respectively) whereas there was no significant difference between GD and HT patients (p > 0.05). There was a correlation between decreased ICAM-1 methylation and exophthalmos (p = 0.01) and the high TSI level (p < 0.002) in GD patients. However, there was no correlation between ICAM-1 methylation and other clinicopathological features or other laboratory parameters in GD or HT. Furthermore, ICAM-1 mRNA expression showed significant up-regulation in ICAM-1 un-methylated samples compared to methylated samples in both GD and HT patients (p < 0.001 for each). Results provided the evidence of association of the hypo-methylation status of ICAM-1 gene promoter with GD and HT patients. In addition, DNA methylation may have a critical role in the ICAM-1 expression regulation of AITD patients.
Assuntos
Metilação de DNA/genética , Molécula 1 de Adesão Intercelular/genética , Tireoidite Autoimune/genética , Adulto , Epigênese Genética/genética , Feminino , Regulação da Expressão Gênica/genética , Doença de Graves/genética , Doença de Hashimoto/genética , Humanos , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Regiões Promotoras Genéticas/genética , Tireoidite Autoimune/metabolismoRESUMO
BACKGROUND: Incretins have opened a new era in type 2 diabetes mellitus (T2DM) pathogenesis. The present study aimed to assess whether there is an association between GIPR rs2302382, GIPR rs1800437 and GLP-1R rs367543060 polymorphisms with T2DM or not and also to determine the effect of these polymorphisms on gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) levels. METHODS: One hundred and fifty T2DM patients and 150 healthy controls were included in the study. Polymorphisms of GIPR rs1800437, GIPR rs2302382 and GLP-1R rs367543060 were genotyped using restriction fragment length polymorphism (RFLP)-polymerase chain reaction (PCR), multiplex allele-specific PCR and RFLP-PCR respectively. GIP and GLP levels were measured by an enzyme-linked immunosorbent assay. RESULTS: We found a significant association of both the homozygous AA and the minor allele A of GIPR rs2302382 with T2DM. The frequency of haplotype C(rs2302382) G(rs1800437) was significantly higher in controls than in diabetics; odds ratio (95% confidence interval): 1.99 (1.44-2.75) (p < 0.001), whereas the haplotype A(rs2302382) C(rs1800437) was significantly higher in patients than controls. We did not find any association of GLP-1R rs367543060 polymorphism with T2DM. We found a significant increase in serum total GIP and a significant decrease of GLP-1 levels in T2DM patients. CONCLUSIONS: We reveal for the first time an association between the GIPR rs2302382 polymorphism and T2DM in Egyptians. Yet, there was no significant association of GIPR rs1800437 or GLP-1R rs367543060 with T2DM risk. The haplotype A (rs2302382) C (rs1800437) was associated with an increased risk of T2DM. Furthermore, there was a significant increase of GIP and a significant decrease of GLP-1 levels when diabetic patients were compared with controls. An important finding was that there was a relationship between both GIPR rs2302382 and rs1800437 variants and their cognate ligand levels.
Assuntos
Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Receptores de Peptídeos Semelhantes ao Glucagon/genética , Polimorfismo Genético , Receptores dos Hormônios Gastrointestinais/genética , Adulto , Alelos , Biomarcadores , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Egito/epidemiologia , Feminino , Frequência do Gene , Genótipo , Receptores de Peptídeos Semelhantes ao Glucagon/sangue , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Osteopenia and osteoporosis are considered major health problems in patients suffering from thalassemia due to increased life expectancy of those patients. Osteoprotegerin (OPG) and receptor activator of NF-kappa-B ligand (RANKL) have been recently implicated in the pathogenesis of various types of osteoporosis. The aim of this study is to evaluate the role of serum OPG/RANKL ratio in patients suffering from thalassemia complicated with osteoporosis. Serum OPG and RANKL were measured in thalassemia patients and 20 healthy control subjects, using ELISA methods. Stastistically, the results demonstrate lower OPG and OPG/RANKL ratio in patients suffering from thalassemia with documented osteopenia or osteoporosis in comparison with control group and patients suffering from thalassemia without osteopenia or osteoporosis. OPG/RANKL ratio could become a promising rapid and cheap screening marker for osteopenia or osteoporosis in patients suffering from thalassemia. Furthermore, OPG may become a therapeutic option in treatment of osteoporosis of various etiologies including thalassemia.