Receptor for advanced glycation end-product (RAGE) gene polymorphism 2245G/A is associated with pro-inflammatory,oxidative-glycation markers and sRAGE in diabetic retinopathy |
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Authors: | Zhi Xiang Ng Umah Rani Kuppusamy Tajunisah Iqbal Kek Heng Chua |
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Institution: | 1. Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia;2. Department of Ophthalmology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia |
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Abstract: | BackgroundReceptor 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.AimThis study aims to investigate the relationship between 2245G/A RAGE gene polymorphism and selected pro-inflammatory, oxidative-glycation markers in DR patients.MethodsA total of 371 unrelated type 2 diabetic patients 200 with retinopathy, 171 without retinopathy (DNR)] and 235 healthy subjects were recruited. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism method followed by DNA sequencing. The nuclear and cytosolic extracts from peripheral blood mononuclear cells were used for nuclear factor kappa B (NF-κB) p65 and superoxide dismutase activity measurement respectively. Plasma was used for glutathione peroxidase activity, advanced oxidation protein product (AOPP), monocyte chemoattractant protein (MCP)-1, pentosidine and soluble RAGE (sRAGE) measurements.ResultsDR patients with 2245GA genotype had significantly elevated levels of activated NF-κB p65, plasma MCP-1, AOPP and pentosidine but lower level of sRAGE when compared to DR patients with wild-type 2245GG.ConclusionThe RAGE gene polymorphism 2245G/A is associated with pro-inflammatory, oxidative-glycation markers and circulating sRAGE in DR patients. Patients with 2245GA RAGE genotype could aggravate DR possibly via NF-κB mediated inflammatory pathway. |
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Keywords: | AGE Advanced glycation end-product ALT Alanine aminotransferase AOPP Advanced oxidation protein product AST Aspartate aminotransferase AU Arbitrary unit BMI Body mass index DBP Diastolic blood pressure DNA Deoxyribonucleic acid DNR Diabetic non-retinopathy DR Diabetic retinopathy ELISA Enzyme-linked immunosorbent assay GPx Glutathione peroxidase HbA1c Glycated hemoglobin HDL-C High density lipoprotein HWE Hardy Weinberg equilibrium LDL-C Low density lipoprotein MCP-1 Monocyte chemoattractant protein-1 NF-κB Nuclear factor kappa B NPDR Non-proliferative diabetic retinopathy PBMC Peripheral blood mononuclear cell PDR Proliferative diabetic retinopathy RAGE Receptor for advanced glycation end-product SBP Systolic blood pressure SD Standard deviation SNP Single nucleotide polymorphism SOD Superoxide dismutase sRAGE Soluble RAGE |
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