JPMA-2020-01-184 Association analysis of -429T/C receptor for advanced glycation end products (RAGE) gene polymorphism with type 2 diabetic retinopathy and serum soluble RAGE levels in Pakistani patients

2020 ◽  
pp. 1-16
Author(s):  
Shazia Qayyum ◽  
Muhammad Afzal ◽  
Abdul Khaliq Naveed ◽  
Admin
Keyword(s):  
Diabetic Retinopathy ◽  
Gene Polymorphism ◽  
Advanced Glycation End Products ◽  
Enzyme Linked Immunosorbent Assay ◽  
Advanced Glycation ◽  
Allelic Frequencies ◽  
Soluble Rage ◽  
Glycation End Products ◽  
End Products

Abstract Objective: To investigate the association of receptor for advanced glycation end products (RAGE) gene polymorphism 429T/C (rs1800625) with diabetic retinopathy (DR) and serum soluble RAGE (sRAGE) levels in Pakistani patients with Type 2 diabetes. Methods: A case-control study, conducted from January 2017 to December 2018, including 150 healthy controls (HC), 150 diabetics without retinopathy (DWR) and 150 DR patients. Ethical approval was taken from Ethics Review Committee of Islamic International Medical College - Riphah International University (RIU). Genotyping for 429T/C was done by Tetra-primer amplification refractory mutation system – polymerase chain reaction (T-ARMS-PCR). Serum sRAGE levels were measured by enzyme-linked immunosorbent assay (ELISA). Data was analysed to calculate descriptive and inferential statistics to compare genotype/allelic frequencies, biochemical markers and serum sRAGE among three study groups. Results: The frequency of TT, TC and CC genotypes of 429T/C polymorphism were: 91.3%, 6.7%, 2% in HC, 88.6%, 8.7%, 2.7% in DWR and 84.7%, 12.0%, 3.3 % in DR groups. No significant association of 429T/C genotypic and allelic frequencies with DWR and DR along with its subtypes, non- proliferative (NPDR) and proliferative (PDR) was observed. Upon further stratifying NPDR into mild, moderate and severe, an association of heterozygous TC with severe NPDR was observed compared to DWR in univariate and multinomial regression analysis. Serum sRAGE levels were significantly high in PDR patients compared to DWR and were positively correlated with fasting plasma glucose (FPG) in DR group.  

scholarly journals Association analysis of 374T/A (rs1800624) receptor for advanced glycation end-products (RAGE) gene polymorphism with diabetic retinopathy in Pakistani patients

2021 ◽  
Vol 37 (3) ◽  
Author(s):  
Shazia Qayyum ◽  
Muhammad Afzal ◽  
Abdul Khaliq Naveed
Keyword(s):  
Diabetic Retinopathy ◽  
Gene Polymorphism ◽  
Association Analysis ◽  
Advanced Glycation End Products ◽  
Fundus Photography ◽  
Amplification Refractory Mutation System ◽  
Advanced Glycation ◽  
Soluble Rage ◽  
Glycation End Products ◽  
End Products

Objectives: to determine the relationship of 374T/A (rs1800624) polymorphism in the gene encoding RAGE with Type-2 diabetes mellitus (T2DM), diabetic retinopathy (DR) and serum soluble RAGE (sRAGE) level in Pakistani patients. Methods: A case-control study, conducted from January 2017 to December 2018, involving 150 healthy controls (HC), 150 T2DM patients with no retinopathy (DNR) and 150 DR patients diagnosed by coloured fundus photography. Tetra-primer amplification refractory mutation system – polymerase chain reaction (T-ARMS-PCR) was used for genotyping. Serum sRAGE levels were measured by enzyme-linked immunosorbent assays (ELIZA). Results: The frequency of TT, TA and AA genotypes of rs1800624 polymorphism were: 92.7%, 6%, 1.3% in HC, 80%, 17.3%, 2.7% in DNR and 76.7%, 19.3%, 4.3% in DR groups. Heterozygous TA genotype and mutant A allele showed significant association with diabetes and DR vs HC. In dominant model, mutant allele showed significant association with DNR and DR vs HC. No significant association of rs1800624 was detected with DR and its sub-groups, non-proliferative DR (NPDR) and proliferative DR (PDR) vs DNR. Dividing NPDR into mild, moderate and severe, heterozygous TA genotype showed significant association with moderate and severe NPDR vs DNR. In DNR and DR groups, TA genotype was significantly associated with raised sRAGE. Conclusion: rs1800624 RAGE gene polymorphism might be a risk factor for T2DM and NPDR in Pakistani patients. Raised sRAGE levels have a positive correlation with PDR and are associated with heterozygosity of rs1800624 polymorphism in DNR and DR groups doi: https://doi.org/10.12669/pjms.37.3.3670 How to cite this:Qayyum S, Afzal M, Naveed AK. Association analysis of 374T/A (rs1800624) receptor for advanced glycation end-products (RAGE) gene polymorphism with diabetic retinopathy in Pakistani patients. Pak J Med Sci. 2021;37(3):---------.  doi: https://doi.org/10.12669/pjms.37.3.3670 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals Association of the Receptor for Advanced Glycation End Products Gene Polymorphisms and Circulating RAGE Levels with Diabetic Retinopathy in the Chinese Population

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Li Yang ◽  
Qunhong Wu ◽  
Yuan Li ◽  
Xiaohong Fan ◽  
Yanhua Hao ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Advanced Glycation End Products ◽  
Chinese Population ◽  
Genetic Interaction ◽  
Interaction Model ◽  
Serum Levels ◽  
Advanced Glycation ◽  
Soluble Rage ◽  
Glycation End Products ◽  
End Products

Objectives. This study investigated the association between polymorphisms in the receptor for advanced glycation end products (RAGE) gene and the susceptibility to diabetic retinopathy (DR) in a Chinese population and identified a correlation between serum-soluble RAGE (sRAGE) levels and DR risk.Materials and Methods. We enrolled 1040 patients with type 2 diabetes mellitus: 372 patients with DR and 668 without retinopathy (NDR). All polymorphisms were genotyped by time-of-flight mass spectrometry. Serum levels of sRAGE were assayed by enzyme-linked immunosorbent assays. The interaction of SNPs was analyzed by multifactor dimensionality reduction (MDR).Results. The frequency of the SS genotype for the G82S polymorphism was 12.4% in the DR group and 6.6% in the NDR group; this difference was significant. G82S was associated with sRAGE levels. Specifically, after adjustments for age, sex, duration, and glucose metabolism, serum sRAGE levels were significantly higher in DR subjects with the S/S genotype than in NDR subjects in general. In the DR group, subjects with the G/S genotype had lower sRAGE levels than subjects with the G/G or S/S genotype (P<0.01). The best multilocus genetic interaction model was assessed using the MDR method; 2184A/G, 1704G/T, G82S, and −429T/C were identified.Conclusions. The findings suggest that the G82S polymorphism in theRAGEgene is associated with DR risk, and G82S was associated with circulating levels of sRAGE. The mechanism by which G82S polymorphism modulates the sRAGE levels remains to be elucidated.

scholarly journals Circulating soluble receptor for advanced glycation end products and other factors in type 2 diabetes patients with colorectal cancer

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiaohai Zhou ◽  
Ning Lin ◽  
Mingjie Zhang ◽  
Xiaoling Wang ◽  
Ye An ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Type 2 Diabetes ◽  
Total Cholesterol ◽  
Advanced Glycation End Products ◽  
Enzyme Linked Immunosorbent Assay ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Diabetes Patients

Abstract Background Recent study showed that individuals with type 2 diabetes have a high risk of developing colorectal cancer (CRC), in which Receptor for Advanced Glycation End Products (RAGE) plays a pivotal role. We conducted a cross-sectional study to examine the relationships of circulating sRAGE, CRC and other clinical factors in type2 diabetes patients. Methods A total of 150 type 2 diabetes patients aged 50 years and older were enrolled, including 50 patients with CRC and 100 patients without CRC. We measured Serum levels of sRAGE and interleukin-6(IL-6) using an enzyme-linked immunosorbent assay (ELISA). In addition, other clinical parameters were also measured during hospitalization. Results Type 2 diabetes patients with CRC had higher triglyceride, total cholesterol, IL-6, and circulating sRAGE levels and lower use of medicines than type 2 diabetes patients without CRC. Circulating sRAGE was associated with an increased risk for CRC (OR = 2.289 for each SD increase in sRAGE, 95% CI = 1.037–5.051; P = 0.04) among Type 2 diabetes patients after adjustment for confounders. Furthermore, circulating sRAGE levels among type 2 diabetes patients were positively correlated with triglyceride (r = 0.377, P < 0.001), total cholesterol (r = 0.491, P < 0.001), and low-density lipoprotein cholesterol (LDL-c)(r = 0.330, P < 0.001) levels; the homeostatic model assessment for insulin resistance(HOMA-IR)score (r = 0.194, P = 0.017); and fasting serum insulin (r = 0.167, P = 0.041) and IL-6 (r = 0.311, P < 0.001) concentrations. Conclusions Our results suggested that circulating sRAGE is independently risk factor for CRC, and also closely related to inflammation, dyslipidemia in type 2 diabetes patients.

scholarly journals Receptor of advanced glycation end products and cardiovascular risk in elderly with type 2 diabetes mellitus

2018 ◽  
Vol 90 (2) ◽  
Author(s):  
Claudia Borsa ◽  
Daniela Gradinaru ◽  
Denisa Margina ◽  
Gabriel Ioan Prada ◽  
Catalina Pena
Keyword(s):  
Cardiovascular Risk ◽  
Advanced Glycation End Products ◽  
Vascular Complications ◽  
Elderly Subjects ◽  
Risk Markers ◽  
Advanced Glycation ◽  
Soluble Rage ◽  
Glycation End Products ◽  
End Products

The interaction of Advanced Glycation End products (AGEs) and their specific receptor, Receptor for Advanced Glycation End products (RAGE) play an important role in diabetes and vascular complications. Engagement of RAGE by AGEs leads to activation of cellular signaling pathways and vascular dysfunction. The soluble RAGE (sRAGE) acts as a decoy receptor for AGEs. The aim of this study was to evaluate the soluble RAGE in elderly subjects with T2DM and its relationships with glycoxidative, inflammatory and cardiovascular risk markers. The serum AGEs, sRAGE, interleukine- 6 (IL-6), lipid profile, glycemic status, uric acid, creatinine and cardiovascular risk markers were determined in elderly subjects with type 2 diabetes mellitus (T2DM, N=72, 75±4 years old) and aged-match healthy subjects (N=15, 76±3 years old). Significant higher levels of AGEs and AGEs/sRAGE ratio concomitantly with significant lower levels of sRAGE were pointed out in elderly subjects with T2DM as compared to control. The values of AGEs/sRAGE ratio were significantly positively associated (P<0.05) with atherogenic, inflammatory and cardiovascular risk markers and significantly negatively with anti-atherogenic lipoproteins (P<0.05). The multivariate regression analyses showed that atherogenic index was an independent predictor of sRAGE levels and AGEs/sRAGE ratio values. The associations of soluble RAGE and the AGEs/sRAGE ratio with atherogenic and inflammatory markers could reflect the protective role of soluble variants of RAGE in atherosclerosis and diabetes vascular complications.

scholarly journals Diabetic Retinopathy and Skin Tissue Advanced Glycation End Products Are Biomarkers of Cardiovascular Events in Type 2 Diabetic Patients

2021 ◽  
Vol 11 (12) ◽  
pp. 1344
Author(s):  
Alejandra Planas ◽  
Olga Simó-Servat ◽  
Cristina Hernández ◽  
Ángel Ortiz-Zúñiga ◽  
Joan Ramón Marsal ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Advanced Glycation End Products ◽  
Cardiovascular Events ◽  
Subcutaneous Tissue ◽  
Diabetic Patients ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

Risk of cardiovascular events is not homogeneous in subjects with type 2 diabetes; therefore, its early identification remains a challenge to be met. The aim of this study is to evaluate whether the presence of diabetic retinopathy and accumulation of advanced glycation end-products in subcutaneous tissue can help identify patients at high risk of cardiovascular events. For this purpose, we conducted a prospective study (mean follow-up: 4.35 years) comprising 200 subjects with type 2 diabetes with no history of clinical cardiovascular disease and 60 non-diabetic controls matched by age and sex. The primary outcome was defined as the composite of myocardial infarction, coronary revascularization, stroke, lower limb amputation or cardiovascular death. The Cox proportional hazard multiple regression analysis was used to determine the independent predictors of cardiovascular events. The patients with type 2 diabetes had significantly more cardiovascular events than the non-diabetic subjects. Apart from the classic factors such as age, sex and coronary artery calcium score, we observed that the diabetic retinopathy and advanced glycation end-products in subcutaneous tissue were independent predictors of cardiovascular events. We conclude that the diabetic retinopathy and advanced glycation end-products in subcutaneous tissue could be useful biomarkers for selecting type 2 diabetic patients in whom the screening for cardiovascular disease should be prioritized, thereby creating more personalized and cost-effective medicine.

scholarly journals Experimental Hyperglycemia Alters Circulating Concentrations and Renal Clearance of Oxidative and Advanced Glycation End Products in Healthy Obese Humans

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 532 ◽  
Author(s):  
Ryan Perkins ◽  
Edwin Miranda ◽  
Kristian Karstoft ◽  
Paul Beisswenger ◽  
Thomas Solomon ◽  
...  
Keyword(s):  
Renal Clearance ◽  
Advanced Glycation End Products ◽  
Fractional Excretion ◽  
Methionine Sulfoxide ◽  
Enzyme Linked Immunosorbent Assay ◽  
Advanced Glycation ◽  
Soluble Rage ◽  
Glycation End Products ◽  
End Products

The purpose of this investigation was to evaluate the effects of experimental hyperglycemia on oxidative damage (OX), advanced glycation end products (AGEs), and the receptor for AGEs (RAGE) through an in vivo approach. Obese subjects (n = 10; 31.2 ± 1.2 kg·m−2; 56 ± 3 years) underwent 24 h of hyperglycemic clamp (+5.4 mM above basal), where plasma at basal and after 2 h and 24 h of hyperglycemic challenge were assayed for OX (methionine sulfoxide, MetSO, and aminoadipic acid, AAA) and AGE-free adducts (Ne-carboxymethyllysine, CML; Ne-carboxyethyllysine, CEL; glyoxal hydroimidazolone-1, GH-1; methylglyoxal hydroimidazolone-1, MG-H1; and 3-deoxyglucosone hydroimidazolone, 3DG-H) via liquid chromatography–tandem mass spectrometry (LC–MS/MS). Urine was also analyzed at basal and after 24 h for OX and AGE-free adducts and plasma soluble RAGE (sRAGE) isoforms (endogenous secretory RAGE, esRAGE, and cleaved RAGE, cRAGE), and inflammatory markers were determined via enzyme-linked immunosorbent assay (ELISA). Skeletal muscle tissue collected via biopsy was probed at basal, 2 h, and 24 h for RAGE and OST48 protein expression. Plasma MetSO, AAA, CEL, MG-H1, and G-H1 decreased (−18% to −47%; p < 0.05), while CML increased (72% at 24 h; p < 0.05) and 3DG-H remained unchanged (p > 0.05) with the hyperglycemic challenge. Renal clearance of MetSO, AAA, and G-H1 increased (599% to 1077%; p < 0.05), CML decreased (−30%; p < 0.05), and 3DG-H, CEL, and MG-H1 remained unchanged (p > 0.05). Fractional excretion of MetSO, AAA, CEL, G-H1, and MG-H1 increased (5.8% to 532%; p < 0.05) and CML and 3DG-H remained unchanged (p > 0.05). Muscle RAGE and OST48 expression, plasma sRAGE, IL-1β, IL-1Ra, and TNFα remained unchanged (p > 0.05), while IL-6 increased (159% vs. basal; p > 0.05). These findings suggest that individuals who are obese but otherwise healthy have the capacity to prevent accumulation of OX and AGEs during metabolic stress by increasing fractional excretion and renal clearance.

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