The Association Between Variants of Receptor for Advanced Glycation End Products (RAGE) Gene Polymorphisms and Age-Related Macular Degeneration

Abstract This study investigated the effect of glucose and fructose, and advanced glycation end-products (AGEs) on genome damage in WIL2-NS cells, measured using the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. The effect of AGEs was investigated using the bovine serum albumin (AGE-BSA) model system induced either with glucose (Glu–BSA) or with fructose (Fru–BSA). Liquid chromatography-mass spectrometry (LC-MS/MS) analysis showed higher Nε-carboxymethyllysine (CML; 26.76 ± 1.09 nmol/mg BSA) levels in the Glu–BSA model. Nε-Carboxyethyllysine (CEL; 7.87 ± 0.19 nmol/mg BSA) and methylglyoxal-derived hydroimidazolone-1 (MG-H1; 69.77 ± 3.74 nmol/mg BSA) levels were higher in the Fru–BSA model. Genotoxic effects were measured using CBMN-Cyt assay biomarkers [binucleated(BN) cells with micronuclei (MNi), BN with nucleoplasmic bridges (NPBs) and BN with nuclear buds (NBuds)] following 9 days of treatment with either glucose, fructose, Glu–BSA or Fru–BSA. Fructose treatment exerted a significant genotoxic dose–response effect including increases of BN with MNi (R2 = 0.7704; P = 0.0031), BN with NPBs (R2 = 0.9311; P < 0.0001) and BN with NBuds (R2 = 0.7118; P = 0.0091) on cells, whereas the DNA damaging effects of glucose were less evident. High concentrations of AGEs (400–600 µg/ml) induced DNA damage; however, there was no effect on cytotoxicity indices (necrosis and apoptosis). In conclusion, this study demonstrates a potential link between physiologically high concentrations of reducing sugars or AGEs with increased chromosomal damage which is an important emerging aspect of the pathology that may be induced by diabetes. Ultimately, loss of genome integrity could accelerate the rate of ageing and increase the risk of age-related diseases over the long term. These findings indicate the need for further research on the effects of glycation on chromosomal instability and to establish whether this effect is replicated in humans in vivo.

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Distribution of the Receptor for Advanced Glycation End Products Gene Polymorphisms in Patients With Chronic Periodontitis: A Preliminary Study

Journal of Periodontology ◽

10.1902/jop.2001.72.12.1742 ◽

2001 ◽

Vol 72 (12) ◽

pp. 1742-1746 ◽

Cited By ~ 29

Author(s):

Lydie Izakovičová Hollá ◽

Kateřina Kaňková ◽

Antonín Fassmann ◽

Dana Bučková ◽

Tomáš Halabala ◽

...

Keyword(s):

Advanced Glycation End Products ◽

Chronic Periodontitis ◽

Gene Polymorphisms ◽

Advanced Glycation ◽

Glycation End Products ◽

End Products ◽

Preliminary Study

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The association between dietary and skin advanced glycation end products: the Rotterdam Study

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqaa117 ◽

2020 ◽

Vol 112 (1) ◽

pp. 129-137 ◽

Cited By ~ 1

Author(s):

Jinluan Chen ◽

Komal Waqas ◽

Robby Carlo Tan ◽

Trudy Voortman ◽

M Arfan Ikram ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Advanced Glycation End Products ◽

Time Difference ◽

European Ancestry ◽

Rotterdam Study ◽

Advanced Glycation ◽

Age Related ◽

Glycation End Products ◽

End Products

ABSTRACT Background Advanced glycation end products (AGEs) accumulate in tissues with age and in conditions such as diabetes mellitus and chronic kidney disease (CKD), and they may be involved in age-related diseases. Skin AGEs measured as skin autofluorescence (SAF) are a noninvasive reflection of long-term AGE accumulation in tissues. Whether AGEs present in the diet (dAGEs) contribute to tissue AGEs is unclear. Objectives Our aim was to investigate the association between dietary and skin AGEs in the Rotterdam Study, a population-based cohort of mainly European ancestry. Methods In 2515 participants, intake of 3 dAGEs [carboxymethyl-lysine (CML), N-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MGH1), and carboxyethyl-lysine (CEL)] was estimated using FFQs and the content of AGEs measured in commonly consumed foods. SAF was measured 5 y (median value) later using an AGE Reader. The association of dAGEs with SAF was analyzed in linear regression models and stratified for diabetes and chronic kidney disease (CKD, defined as estimated glomerular filtration rate ≤60 mL/min) status. Results Mean ± SD intake was 3.40 ±0.89 mg/d for CML, 28.98 ±7.87 mg/d for MGH1, and 3.11 ±0.89 mg/d for CEL. None of them was associated with SAF in the total study population. However, in stratified analyses, CML was positively associated with SAF after excluding both individuals with diabetes and individuals with CKD: 1 SD higher daily CML intake was associated with a 0.03 (95% CI: 0.009, 0.05) arbitrary units higher SAF. MGH1 and CEL intake were not significantly associated with SAF. Nevertheless, the associations were stronger when the time difference between dAGEs and SAF measurements was shorter. Conclusions Higher dietary CML intake was associated with higher SAF only among participants with neither diabetes nor CKD, which may be explained by high AGE formation in diabetes and decreased excretion in CKD or by dietary modifications in these disease groups. The dAGE–SAF associations were also modified by the time difference between measurements. Our results suggest that dAGEs can influence tissue AGE accumulation and possibly thereby age-related diseases. This trial was registered at the Netherlands National Trial Register as NTR6831 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6831) and at the WHO International Clinical Trials Registry Platform as NTR6831 (http://www.who.int/ictrp/network/primary/en/).

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Receptor for advanced glycation end-products (RAGE) - soluble form (sRAGE) and gene polymorphisms in patients with breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.21113 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 21113-21113

Author(s):

P. Tesarova ◽

M. Kalousova ◽

M. Jachymova ◽

O. Mestek ◽

L. Petruzelka ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptors ◽

Advanced Glycation End Products ◽

Gene Polymorphisms ◽

Soluble Form ◽

Healthy Controls ◽

Serum Concentrations ◽

Advanced Glycation ◽

Glycation End Products ◽

End Products

21113 Background: Receptor for advanced glycation end products (RAGE) may be involved in the pathogenesis of the cancer progression and metastasis. Pathological effects mediated via RAGE are physiologically inhibited by soluble RAGE (sRAGE), so the higher sRAGE levels may confer the patients with cancer with better outcome.. Our aim was to study sRAGE and RAGE gene polymorphisms in patients with breast cancer. Methods: We studied sRAGE and RAGE polymorphisms in 120 patients with breast cancer (subdivided based on the clinical stage, histologic grading, expression of hormonal and C-erb B2 receptors) and in 92 healthy controls. Results: Despite higher serum concentrations of AGEs, serum concentrations of sRAGE were lower in patients with breast cancer compared to healthy controls (1581 ± 777 vs. 1803 ± 632 ng/ml, p < 0.05). Serum levels of sRAGE were higher in patients with advanced breast cancer (stage III), lower grade and positive estrogen receptors and intermediate positivity of C-erb B2 (Her-neu) receptors and were also influenced genetically (G82S and 2184 AG polymorphisms of the RAGE gene). Conclusions: Decreased sRAGE levels in patients with breast cancer may contribute to the progression of the disease. Patients with better outcome (with low grade and positive estrogen receptors) have higher sRAGE levels. Progression of the disease, may, however, increase sRAGE levels, possibly as a compensatory mechanism to counteract further progression. No significant financial relationships to disclose.

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