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Association analysis of -429T/C and -374T/A polymorphisms of receptor of advanced glycation end products (RAGE) gene in Malaysian with type 2 diabetic retinopathy

Ng ZX, Kuppusamy UR, Tajunisah I, Fong KC, Chua KH

Diabetes Res Clin Pract, 2012 Mar;95(3):372-7.
PMID: 22154374 DOI: 10.1016/j.diabres.2011.11.005

Conflicting results have been reported in different populations on the association between two particular RAGE gene polymorphisms (-429T/C and -374T/A) and retinopathy in diabetic patients. Therefore this study was designed to assess the association between both gene polymorphisms with retinopathy in Malaysian diabetic patients. A total of 342 type 2 diabetic patients [171 without retinopathy (DNR) and 171 with retinopathy (DR)] and 235 healthy controls were included in this study. Genomic DNA was obtained from blood samples and the screening for the gene polymorphisms was done using polymerase chain reaction-restriction fragment length polymorphism approach. Overall, the genotype distribution for both polymorphisms was not statistically different (p>0.05) among the control, DNR and DR groups. The -429C minor allele frequency of DR group (12.0%) was not significantly different (p>0.05) when compared to DNR group (16.1%) and healthy controls (11.3%). The -374A allele frequency also did not differ significantly between the control and DNR (p>0.05), control and DR (p>0.05) as well as DNR and DR groups (p>0.05). This is the first study report on RAGE gene polymorphism in Malaysian DR patients. In conclusion, -429T/C and -374T/A polymorphisms in the promoter region of RAGE gene were not associated with Malaysian type 2 DR patients.

Matched MeSH terms: Diabetic Retinopathy/genetics*
Circulating miR-3197 and miR-2116-5p as novel biomarkers for diabetic retinopathy

Ji H, Yi Q, Chen L, Wong L, Liu Y, Xu G, et al.

Clin Chim Acta, 2020 Feb;501:147-153.
PMID: 31678272 DOI: 10.1016/j.cca.2019.10.036

Diabetic retinopathy (DR) is the leading cause of vision loss among older adults. The goal of this case-control study was to identify circulating miRNAs for the diagnosis of DR. The miRNeasy Serum/Plasma Kit was used to extract serum miRNAs. The μParaflo™ MicroRNA microarray was used to detect the expression levels of the miRNAs. The miRWalk algorithm was applied to predict the target genes of the miRNAs, which were further confirmed by the dual luciferase reporter gene system in HEK293T cells. A microarray was performed between 5 DR cases and 5 age-, sex-, body mass index-, and duration of diabetes-matched type 2 diabetic (T2DM) controls. The quantitative reverse transcription polymerase chain reaction technique was used to validate the differentially expressed circulating miRNAs in 45 DR cases and 45 well-matched controls. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the circulating miRNAs as diagnostic biomarkers for DR. Our microarray analysis screened out miR-2116-5p and miR-3197 as significantly up-regulated in DR cases compared with the controls. Furthermore, two miRNAs were validated in the 45 DR cases and 45 controls. The ROC analysis suggested that both miR-3197 and miR-2116-5p distinguished DR cases from controls. An additional dual-luciferase reporter gene assay confirmed that notch homolog 2 (NOTCH2) was the target gene of miR-2116-5p. Both miR-3197 and miR-2116-5p were identified as promising diagnostic biomarkers for DR. Future research is still needed to explore the molecular mechanisms of miR-3197 and miR-2116-5p in the pathogenesis of DR.

Matched MeSH terms: Diabetic Retinopathy/genetics*
Fulltext Lack of association between Gly82Ser, 1704G/T and 2184A/G of RAGE gene polymorphisms and retinopathy susceptibility in Malaysian diabetic patients

Ng ZX, Kuppusamy UR, Poh R, Tajunisah I, Koay AC, Fong KC, et al.

Genet. Mol. Res., 2012 Mar 01;11(1):455-61.
PMID: 22427038 DOI: 10.4238/2012.March.1.2

Diabetic retinopathy is the most common diabetic eye disease, occurring in about 60% of type 2 diabetic patients. Other than known clinical risk factors, the influence of genes has been suggested as part of the development of diabetic retinopathy. We investigated the association of Gly82Ser, 1704G/T and 2184A/G polymorphisms in the RAGE gene with retinopathy in type 2 diabetic patients in Malaysia. Ninety-eight unrelated retinopathy patients and 185 unrelated healthy controls from all over Malaysia were recruited in this study. The allele and genotype frequencies of the three gene polymorphisms were investigated using PCR-RFLP. The allele frequency of the three polymorphisms did not differ significantly between the control and the retinopathy group (P > 0.05). Analysis of the frequency of GA+AA, GT+TT and AG+GG in the retinopathy group did not reveal significant differences (P > 0.05) compared to the control group. We conclude that RAGE gene Gly82Ser, 1704G/T and 2184A/G polymorphisms are not associated with retinopathy development in the Malaysian population.

Matched MeSH terms: Diabetic Retinopathy/genetics*
Fulltext Exosomal MicroRNA-15a Transfer from the Pancreas Augments Diabetic Complications by Inducing Oxidative Stress

Kamalden TA, Macgregor-Das AM, Kannan SM, Dunkerly-Eyring B, Khaliddin N, Xu Z, et al.

Antioxid Redox Signal, 2017 Nov 01;27(13):913-930.
PMID: 28173719 DOI: 10.1089/ars.2016.6844

AIMS: MicroRNAs (miRNAs), one type of noncoding RNA, modulate post-transcriptional gene expression in various pathogenic pathways in type 2 diabetes (T2D). Currently, little is known about how miRNAs influence disease pathogenesis by targeting cells at a distance. The purpose of this study was to investigate the role of exosomal miRNAs during T2D.
RESULTS: We show that miR-15a is increased in the plasma of diabetic patients, correlating with disease severity. miR-15 plays an important role in insulin production in pancreatic β-cells. By culturing rat pancreatic β-cells (INS-1) cells in high-glucose media, we identified a source of increased miR-15a in the blood as exosomes secreted by pancreatic β-cells. We postulate that miR-15a, produced in pancreatic β-cells, can enter the bloodstream and contribute to retinal injury. miR-15a overexpression in Müller cells can be induced by exposing Müller cells to exosomes derived from INS-1 cells under high-glucose conditions and results in oxidative stress by targeting Akt3, which leads to apoptotic cell death. The in vivo relevance of these findings is supported by results from high-fat diet and pancreatic β-cell-specific miR-15a-/- mice.
INNOVATION: This study highlights an important and underappreciated mechanism of remote cell-cell communication (exosomal transfer of miRNA) and its influence on the development of T2D complications.
CONCLUSION: Our findings suggest that circulating miR-15a contributes to the pathogenesis of diabetes and supports the concept that miRNAs released by one cell type can travel through the circulation and play a role in disease progression via their transfer to different cell types, inducing oxidative stress and cell injury. Antioxid. Redox Signal. 27, 913-930.

Matched MeSH terms: Diabetic Retinopathy/genetics*
Fulltext 2245G/A polymorphism of the receptor for advanced glycation end-products (RAGE) gene is associated with diabetic retinopathy in the Malaysian population

Ng ZX, Kuppusamy UR, Tajunisah I, Fong KC, Koay AC, Chua KH

Br J Ophthalmol, 2012 Feb;96(2):289-92.
PMID: 22116960 DOI: 10.1136/bjophthalmol-2011-300658

The receptor for advanced glycation end-products (RAGE) has been implicated in the pathogenesis of diabetic microvascular complications. The aim of this study was to investigate the association between 2245G/A gene polymorphism of the RAGE gene and retinopathy in Malaysian type 2 diabetic patients.

Matched MeSH terms: Diabetic Retinopathy/genetics*
Investigation of SLC2A1 26177A/G gene polymorphism via high resolution melting curve analysis in Malaysian patients with diabetic retinopathy

Ng ZX, Kuppusamy UR, Tajunisah I, Fong KC, Chua KH

J Diabetes Complications, 2012 Sep-Oct;26(5):388-92.
PMID: 22795339 DOI: 10.1016/j.jdiacomp.2012.05.014

PURPOSE:
In this study, we aimed to investigate the possible association between SLC2A1 26177A/G polymorphism and diabetic retinopathy (DR) in Malaysian patients with type 2 diabetes.

METHODS:
Genomic DNA was extracted from 211 Malaysian type 2 diabetic patients (100 without retinopathy [DNR], 111 with retinopathy) and 165 healthy controls. A high resolution melting assay developed in this study was used to detect SLC2A1 26177A/G polymorphism followed by statistical analysis.

RESULTS:
A statistically significant difference in 26177G minor allele frequency between healthy controls (19.7 %) and total patient group (26.1 %) (p<0.05, Odd ratio = 1.437, 95% Confidence interval = 1.015-2.035) as well as between healthy controls (19.7 %) and DNR patients (27.5%) (p<0.05, Odd ratio = 1.546, 95% Confidence interval = 1.024-2.336) was shown in this study. However, when compared between DR and DNR patients, there was no significant difference (p>0.05).

CONCLUSIONS:
This is the first study which shows that SLC2A1 26177G allele is associated with type 2 diabetes in Malaysian population but not with DR.

Matched MeSH terms: Diabetic Retinopathy/genetics*
Receptor for advanced glycation end-product (RAGE) gene polymorphism 2245G/A is associated with pro-inflammatory, oxidative-glycation markers and sRAGE in diabetic retinopathy

Ng ZX, Kuppusamy UR, Iqbal T, Chua KH

Gene, 2013 Jun 1;521(2):227-33.
PMID: 23545311 DOI: 10.1016/j.gene.2013.03.062

Receptor for advanced glycation end-product (RAGE) gene polymorphism 2245G/A is associated with diabetic retinopathy (DR). However, the mechanism on how it affects the disease development is still unclear.

Matched MeSH terms: Diabetic Retinopathy/genetics*