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 ◽  
...  

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.

Author(s):  
Shazia Qayyum ◽  
Muhammad Afzal ◽  
Abdul Khaliq Naveed ◽  
Admin

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.  


Author(s):  
Kosuke Saku ◽  
Nobuhiro Tahara ◽  
Tohru Takaseya ◽  
Hiroyuki Otsuka ◽  
Kazuyoshi Takagi ◽  
...  

Background Aortic stenosis ( AS ) is highly prevalent in patients with atherosclerotic cardiovascular disease. Advanced glycation end products ( AGE s) and the receptor for AGE s ( RAGE ) play a pivotal role for vascular calcification in atherosclerosis. We hypothesize that the AGEs– RAGE axis could also be involved in the pathophysiological mechanism of calcified AS . Methods and Results A total of 54 patients with calcified AS who underwent aortic valve replacement were prospectively enrolled from 2014 to 2016 (mean age 75.3±7.7 years). Aortic valve specimens were obtained from 47 patients and 16 deceased control subjects without aortic valve disease (mean age 63.2±14.5 years). The valvular expression of RAGE was evaluated by immunohistochemistry. Serum levels of AGE s and soluble RAGE were measured in 50 patients with calcified AS and 70 age‐matched and sex‐matched control subjects without heart disease. The valvular RAGE expression in patients with calcified AS was higher than controls ( P =0.004) and was significantly associated with a decreased ankle‐brachial pressure index ( P =0.007) and an increased intima‐media thickness ( P =0.026). RAGE and α–smooth muscle actin were coexpressed and were partially costained with osteocalcin and alkaline phosphatase. The serum levels of AGE s and soluble RAGE were significantly higher in the patients with calcified AS than in the controls ( P =0.013 and P <0.001, respectively). Soluble RAGE (inversely) and use of aspirin were independently correlated with changes in left ventricular systolic function after aortic valve replacement ( P =0.012 and P =0.002, respectively). Conclusions Our present study suggests that RAGE may play a role in the pathogenesis of calcified AS , which is a prognostic marker in patients with AS after aortic valve replacement.


2021 ◽  
Vol 37 (3) ◽  
Author(s):  
Shazia Qayyum ◽  
Muhammad Afzal ◽  
Abdul Khaliq Naveed

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.


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 275-LB
Author(s):  
EDWIN R. MIRANDA ◽  
JR. KELLY N. FULLER ◽  
RYAN PERKINS ◽  
PAUL J. BEISSWENGER ◽  
SARAH S. FARABI ◽  
...  

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Justina Owusu ◽  
Fatma Huffman ◽  
Juan Liuzzi ◽  
Tan Li ◽  
Vijaya Narayanan

Abstract Objectives Advanced Glycation End Products, (AGEs) and their soluble receptor (sRAGE) have been implicated in the development of complications and mortality among individuals with type 2 diabetes (T2D). There is limited information on the relationship between AGEs and sRAGE and risk of cardiovascular diseases (CVD) in minority groups, who have a higher burden of T2D. The relationship between AGEs and sRAGE and CVD risks in adults with T2D and vitamin D insufficiency/deficiency was assessed in a minority population. Methods A cross sectional study of Hispanics and African Americans with T2D (n = 64, 41 women and 23 men, mean age = 54 ± 9) recruited from two clinics in Miami Dade. Systolic (SBP) and diastolic blood pressure (DBP), weight and height measurement and serum lipid profile were completed. ELISA kits were used to assess serum levels of AGEs (Biotang Inc/TSZ Elisa, Waltham, MA, USA) and sRAGE (Biotang Inc/TSZ Elisa, Waltham, MA, USA). Multiple linear regression was used to assess association between AGEs, sRAGE and CVD risks. Results A negative and significant association between AGEs and high-density lipoprotein cholesterol (HDL-C)(B = −0.551, P = 0.029) was found. The relationship between AGEs and HDL-C persisted after adjusting for covariates (P < 0.05). sRAGE was significantly associated with SBP (B = 0.015, P = 0.025) and diastolic blood pressure DBP (B = 0.0271, P = 0.037). Results loss significance when association between sRAGE and DBP and SBP were adjusted for covariates such as age, body mass index (BMI), smoking and alcohol intake. Conclusions Our results suggest that AGEs and sRAGE are related to markers of cardiovascular risk such as HDL-C, SBP and DBP in the study population of African Americans and Hispanics with T2D and vitamin D insufficiency/deficiency. Measures on reducing serum levels of AGEs and improving sRAGE and vitamin D are warranted in these populations for risk reduction of CVD. Funding Sources Partial funding for this research was provided through an NIH/NIDDK sponsored grant.


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