Methylation Profile of miR-9-1 and miR-9-1/-9-3 as Potential Biomarkers of Diabetic Retinopathy.

AIMS: Analysis of the relationship between the methylation profile of miR-9-1 or miRs -9-1 / -9-3 and diabetic retinopathy. BACKGROUND: Diabetic Retinopathy (DR) is a frequent complication of Diabetes mellitus and it has a decisive impact on the quality of life, as it is one of the biggest causes of blindness in the adult population. Levels of microRNA-9 have been shown to be related to diabetes but little is known about its involvement with DR in humans. OBJECTIVE: To analyze the relationship between the methylation profile of miR-9-1 or miRs -9-1/-9-3 and DR. METHODS: 103 patients diagnosed with diabetes for 5 to 10 years were analyzed. The data were categorized according to clinical, biochemical, lifestyle and anthropometric parameters. DNA extracted from leukocyte samples was used to determine the methylation profile of miRs-9-1 and -9-3 using a specific methylation PCR assay. RESULTS: miR-9-1 methylation was related to diabetic retinopathy, indicating that methylation of this miR increases the chances of presenting retinopathy up to 5 times. In our analyses, diabetics with lower levels of creatinine and CRP showed significant reductions (99% and 97%) in presenting DR. Methylation of both miRs-9-1 and 9-3 methylated increases the chances of presenting DR by 8 times; in addition, a sedentary lifestyle can increase the risk for the same complication by up to 6 times. CONCLUSION: Our results suggest that both methylation of miR-9-1 and e miRs-9-1 / 9-3 favors DR in patients with diabetes in a period of 5 to 10 years of diagnosis.

Physical Activity Level Influences MTHFR Gene Methylation Profile in Diabetic Patients.

INTRODUCTION: MTHFR methylation status is associated with microvascular complications in diabetes, but the factors influencing this profile remain unknown. OBJECTIVE: The aim of this study was to evaluate the influence of physical activity level and nutritional status on the methylation profile of the MTHFR gene in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 111 patients, 43 men and 68 women diagnosed with DM (7.0 ± 2.3 years), answered the International Physical Activity Questionnaire (IPAQ) and underwent blood collection for biochemical analysis, DNA extraction, and MTHFR gene methylation profile determination. RESULT: The comparison of the methylation pattern showed that the partially methylated profile predominates in the insufficiently active group (85%), which does not occur in the sufficiently active group (54%) (p = 0.012). No differences were found in the nutritional status comparison. Logistic regression including overweight, waist circumference, gender, age, time of DM, hypertension, dyslipidemia, smoking, alcoholism, and family DM revealed that the association of the level of physical activity with methylation profile proved to be independent of these confounding variables. Considering the partially methylated profile as a result, being physically inactive favors the partially methylated MTHFR pattern in patients with DM. CONCLUSION: We concluded that insufficient physical activity is associated with partially methylated pattern of MTHFR promoter.

The importance of histopathology in the diagnosis of isolated renal sarcoidosis: a case report / A importância da histopatologia no diagnóstico de sarcoidose renal isolada: um relato de caso

ABSTRACT Introduction: Sarcoidosis is a systemic inflammatory disease of unknown etiology, characterized by the presence of non-caseating granulomas in several organs; renal impairment alone is a rare condition. When it affects the kidneys, the most prevalent manifestations are hypercalcemia and hypercalciuria. This paper aims to address the topic of renal sarcoidosis, by means of a case report, and reinstate the importance of histopathology in its diagnosis. Methods: The data came from an observational clinical study with a qualitative approach, through an interview with the renal sarcoidosis patient and data from her medical records. Case report: Patient D.M.S., 50 years old, Caucasian, presented with reddish eyes and body pains lasting for fifteen days as first manifestations of the disease. Upon kidney ultrasound scan, we found renal parenchymal nephropathy. Serial renal function and metabolic tests reported anemia and progressive urea and creatinine changes, as well as hypercalcemia and hypercalciuria, confirming acute kidney failure (AKF). A histopathological examination suggested the diagnosis, which was confirmed by clinical, laboratory and histopathological data. There was therapeutic resolution after steroid therapy. Discussion: The symptomatology of sarcoidosis is diverse and often non-specific. Renal manifestation, which usually occurs after organ involvement, is present in less than 5% of patients, and about 1% to 2% of these patients may develop AKF. Conclusions: The use of histopathology together with clinical and laboratory data to diagnose isolated renal sarcoidosis, rule out other etiologies and introduce early treatment is of paramount importance.

RESUMO Introdução: A sarcoidose é uma doença inflamatória sistêmica de etiologia desconhecida caracterizada pela presença de granulomas não caseosos em diversos órgãos, sendo raro o comprometimento puramente renal. Quando acomete os rins, as manifestações mais prevalentes são hipercalcemia e hipercalciúria. Este trabalho objetiva abordar o tema sarcoidose renal, por meio de relato de caso, e reafirmar a importância da histopatologia no diagnóstico. Métodos: Os dados foram obtidos por estudo clínico observacional com abordagem qualitativa, por meio de entrevista com a paciente portadora de sarcoidose renal e dados de seu prontuário médico. Relato de caso: Paciente D.M.S., 50 anos, caucasiana, apresentou como primeiras manifestações da doença olhos avermelhados e dores no corpo com duração de quinze dias. Em ultrassonografia renal, foi constatada nefropatia parenquimatosa renal bilateral. Testes seriados de função e metabolismo renal relataram anemia e alteração progressiva de ureia e creatinina, além de hipercalcemia e hipercalciúria, constatando quadro de insuficiência renal aguda (IRA). Foi indicado exame histopatológico que sugeriu o diagnóstico, confirmado pelos dados clínicos, laboratoriais e histopatológico somados. Houve resolução terapêutica após corticoterapia. Discussão: A sintomatologia da sarcoidose é diversificada e, muitas vezes, inespecífica. A manifestação renal, que ocorre geralmente após o acometimento de outros órgãos, está presente em menos de 5% dos pacientes, e cerca de 1% a 2% destes podem desenvolver IRA. Conclusões: É de suma importância o auxílio da histopatologia somada aos dados clínicos e laboratoriais para diagnóstico de sarcoidose renal isolada, exclusão de outras etiologias e introdução de terapêutica precoce.

The importance of histopathology in the diagnosis of isolated renal sarcoidosis: a case report.

INTRODUCTION: Sarcoidosis is a systemic inflammatory disease of unknown etiology, characterized by the presence of non-caseating granulomas in several organs; renal impairment alone is a rare condition. When it affects the kidneys, the most prevalent manifestations are hypercalcemia and hypercalciuria. This paper aims to address the topic of renal sarcoidosis, by means of a case report, and reinstate the importance of histopathology in its diagnosis. METHODS: The data came from an observational clinical study with a qualitative approach, through an interview with the renal sarcoidosis patient and data from her medical records. CASE REPORT: Patient D.M.S., 50 years old, Caucasian, presented with reddish eyes and body pains lasting for fifteen days as first manifestations of the disease. Upon kidney ultrasound scan, we found renal parenchymal nephropathy. Serial renal function and metabolic tests reported anemia and progressive urea and creatinine changes, as well as hypercalcemia and hypercalciuria, confirming acute kidney failure (AKF). A histopathological examination suggested the diagnosis, which was confirmed by clinical, laboratory and histopathological data. There was therapeutic resolution after steroid therapy. DISCUSSION: The symptomatology of sarcoidosis is diverse and often non-specific. Renal manifestation, which usually occurs after organ involvement, is present in less than 5% of patients, and about 1% to 2% of these patients may develop AKF. CONCLUSIONS: The use of histopathology together with clinical and laboratory data to diagnose isolated renal sarcoidosis, rule out other etiologies and introduce early treatment is of paramount importance.

Hypermethylation in the promoter of the MTHFR gene is associated with diabetic complications and biochemical indicators.

BACKGROUND: DNA methylation is an epigenetic mechanism for regulating the transcription of many genes and has been linked to the development of various diseases. A promising gene to investigate is methylenetetrahydrofolate reductase (MTHFR), since the enzyme methylenetetrahydrofolate reductase (MTHFR) promotes methyl radical synthesis in the homocysteine cycle and can provide methyl groups for DNA methylation. In addition, several studies have correlated gene polymorphisms of this enzyme with a greater risk of diabetes, but little is known regarding the relationship between epigenetic changes in this gene and diabetes and its complications. The aim of this study was to investigate the relationship between methylation profile in the MTHFR gene promoter and biochemical, inflammatory and oxidative stress markers in individuals with type 2 diabetes (T2DM) who have been diagnosed for 5-10 years with or without diabetic retinopathy (DR) and nephropathy (DN). METHODS: Specific PCR for methylation (MSP) was used to analyze MTHFR methylation profile in leucocytes DNA. Biochemical markers (glycemia, glycated hemoglobin, total cholesterol, LDL, HDL, triglycerides, serum creatinine), inflammatory markers (C-reactive protein and alpha-1 acid glycoprotein) and oxidative stress (total antioxidant and malonaldehyde) were determined in peripheric blood samples and microalbuminuria in 24 h urine samples. The X2 and Mann-Whitney statistical tests were performed and p < 0.05 were considered significant. RESULTS: The hypermethylated profile was most frequently observed in individuals with retinopathy (p < 0.01) and was associated with higher total cholesterol and LDL levels (p = 0.0046, 0.0267, respectively). Individuals with DN and hypermethylated profiles had higher levels of alpha-1 acid glycoprotein (p = 0.0080) and total antioxidant capacity (p = 0.0169) compared to subjects without complications. CONCLUSIONS: Hypermethylation in the promoter of the MTHFR gene is associated with the occurrence of DR and with biochemical, inflammatory and oxidative stress parameters in the context of chronic complications.