RESUMO
The receptor for advanced glycation end products (RAGE) is a transmembrane protein that interacts with its ligands, advanced glycation end products (AGEs). AGEs are elevated in diabetes and diabetic complications, leading to increased oxidative stress and activation of pro-inflammatory pathways facilitated by AGE-RAGE signaling. Polymorphisms in the RAGE gene can potentially affect AGE-RAGE interaction and its downstream signaling, which plays a crucial role in the progression of diabetes and its complications. In this study, we used nanopore sequencing for genotyping of RAGE polymorphism and identified a maximum number of 33 polymorphisms, including two previously unreported novel mutations in a cohort of healthy, type 2 diabetics without nephropathy and type 2 diabetics with nephropathy in order to identify associations. Two novel RAGE polymorphisms in the intron 8 and 3'UTR region at genomic locations 32181834 and 32181132, respectively, were detected with a low frequency. For four previously reported polymorphisms, cross-validation by PCR-RFLP showed 99.75% concordance with nanopore sequencing. Analysis of genotype distribution and allele frequencies revealed that five single nucleotide polymorphisms, i.e., rs1800625, rs3131300, rs3134940, rs2070600, and rs9391855, were associated with an increased risk for type 2 diabetes.
RESUMO
C677T (rs1801133) and A1298C (rs1801131) MTHFR gene polymorphisms and/or nutritional deficiency of folate/vitamin B12 leading to hyperhomocysteinemia is an established risk factor for CAD. The objective of this study was to evaluate the clinical usefulness of association between MTHFR C677T (rs1801133) and A1298C (rs1801131) polymorphisms with serum homocysteine, folate and vitamin B12 in addition to conventional cardiovascular risk factors in patients with young CAD. Genomic DNA was isolated from the whole blood. Genotyping of MTHFR C677T (rs1801133) and MTHFR A1298C (rs1801131) polymorphisms in young CAD patients and healthy controls was performed by ARMS-PCR method. Serum homocysteine, vitamin B12 and folate were estimated by CMIA and lipid profile parameters were measured by automated chemistry analyzers. Serum homocysteine levels were significantly higher but serum folate and vitamin B12 levels were not significantly different among young CAD group as compared to control group. Statistically significant hyperhomocysteinemia was observed in carriers of T allele for MTHFR 677C/T (rs1801133) genotype in young CAD group but this association was not significant for MTHFR 1298A/C (rs1801131) polymorphism. The association between hyperhomocysteinemia and CAD in young group was not independent of conventional cardiovascular risk factors. Risk of hyperhomocysteinemia and young CAD could be monitored by MTHFR polymorphism detection followed by serum homocysteine, folate and vitamin B12 measurements. The findings could help to prevent or delay the occurrence of young CAD through appropriate measures.
RESUMO
INTRODUCTION: The impact of CVDs and Type II DM is increasing over the last decade. It has been estimated that by 2025 their incidence will double. Ferritin is one of the key proteins regulating iron homeostasis and is a widely available clinical biomarker of iron status. Some studies suggest that prevalence of atherosclerosis and insulin resistance increases significantly with increasing serum ferritin. Metabolic syndrome is known to be associated with increased risk of atherosclerosis as well as insulin resistance. AIM: The present study was designed to explore the association of serum ferritin levels with metabolic syndrome and insulin resistance. MATERIALS AND METHODS: The present study was prospective, cross sectional. The study protocol was approved by IEC. The study group consisted of 90 participants (50 cases of metabolic syndrome and 40 age and sex matched controls). Diagnosis of metabolic syndrome was done as per NCEP ATP III criteria. Estimation of serum Ferritin and Insulin was done by Chemiluminescence Immunoassay (CLIA) while Glucose by Glucose Oxidase and Peroxidase (GOD-POD) method. Insulin Resistance was calculated by HOMA IR score. STATISTICAL ANALYSIS: Data obtained was statistically analysed by using student t-test. RESULTS: We found statistically significant rise in the levels of serum ferritin (p=<0.001), glucose (p=<0.001), insulin (p=<0.001) and HOMA IR score (p=<0.0001) in cases of metabolic syndrome as compared with controls. CONCLUSION: High serum ferritin levels though within normal range are significantly associated with both metabolic syndrome and insulin resistance.
