The −374A allele of the receptor for advanced glycation end products (RAGE) gene promoter is a protective factor against cardiovascular lesions in type 2 diabetes mellitus patients

Picheth, Geraldo; Costantini, Costantino O.; Pedrosa, Fábio O.; Martinez, Tânia Leme da Rocha; Souza, Emanuel M.

doi:10.1515/cclm.2007.273

Cited by 28 publications

(18 citation statements)

References 21 publications

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“…The close connection between these polymorphic -429C and 2184G alleles has to be pointed out and the same is true for the 2184GG genotype, which it is connected with higher sRAGE and esRAGE levels as well [20] . Concerning cardiovascular risk, the A allele of the -374T/A polymorphism, which was also examined in our study, was associated with a decreased risk for cardiovascular disease in the general population or in diabetic patients [15,17,18,[23][24][25] . The Gly82Ser polymorphism was not associated with cardiovascular disease in the Framingham offspring study [26] as well as in patients with rheumatoid arthritis [27] .…”

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confidence: 51%

Genetic Predisposition to Advanced Glycation End Products Toxicity Is Related to Prognosis of Chronic Hemodialysis Patients

Kalousová¹,

Jáchymová²,

Germanová³

et al. 2010

Kidney Blood Press Res

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Background: Advanced glycation end products (AGEs) belong to uremic toxins and some pathological effects of AGEs are linked to RAGE (receptor for AGEs). Their precursors are detoxified by the glyoxalase (GLO) system. The A419C (E111A) polymorphism of the GLO I gene is associated with vascular disease in hemodialysis (HD) patients and some RAGE gene polymorphisms are implicated in various pathological states. Aim: To study the relationship of A419C GLO I and four RAGE polymorphisms (–429T/C, –374T/A, 2184A/G and Gly82Ser) in the prognosis of HD patients. Methods: The group studied consisted of 214 chronic HD patients prospectively followed up for 43 months. 100 patients died, 48 due to cardiovascular causes. Results: The Kaplan-Meier analysis showed a higher mortality rate in patient-mutated homozygotes for RAGE –429CC, RAGE 2184GG and GLO I 419CC. A higher hazard risk was confirmed by the Cox proportional hazards model when wild-type homozygotes were taken as reference: RAGE –429CC 2.28 (95% CI 1.04–4.99), RAGE 2184GG 3.16 (95% CI 1.44–6.93), and GLO I 419CC 1.75 (95% CI 1.08–2.86). Both RAGE polymorphisms were also associated with cardiovascular mortality: RAGE –429CC 3.54 (95% CI 1.37–9.14) and RAGE 2184GG 5.04 (95% CI 1.93–13.11). Conclusion: In summary, our study shows for the first time a link between RAGE and GLO polymorphisms in the prognosis of HD patients.

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confidence: 51%

Genetic Predisposition to Advanced Glycation End Products Toxicity Is Related to Prognosis of Chronic Hemodialysis Patients

Kalousová¹,

Jáchymová²,

Germanová³

et al. 2010

Kidney Blood Press Res

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“…The functional single nucleotide polymorphisms (SNPs), including variation I codon 82 (G82S, rs 2070600), resulting from the amino acid exchange of glycine for serine in domain V and two polymorphic regions in the promoting region, -429T>C (rs 1800625) and -374T>A (rs 1800624), have been extensively researched in association with pathologies (25) . The allele 374A of RAGE promoter has been associated as a protector against macrovascular damage in patients with DM type 2 (44,55) and the allele -429C with diabetes type 1 (DM1) (56) . More recently, the genome-wide association studies (GWAS) has shown the association of polymorphism G82S with pulmonary function (22) .…”

Section: Rage Gene Structure and Organizationmentioning

confidence: 99%

RAGE receptor and its soluble isoforms in diabetes mellitus complications

Oliveira

Souza

Pedrosa

et al. 2013

J. Bras. Patol. Med. Lab.

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Chronic hyperglycemia, which is present in all types of diabetes, increases the formation of advanced glycation end-products (AGEs). The interaction of AGEs with receptor of advanced glycation end-products (RAGE) initiates a cascade of pro-inflammatory and pro-coagulant processes that result in oxidative stress, stimulating the formation and accumulation of more AGE molecules. This cyclic process, denominated metabolic memory, may explain the persistency of diabetic vascular complications in patients with satisfactory glycemic control. The RAGE found in several cell membranes is also present in soluble isoforms (esRAGE and cRAGE), which are generated by alternative deoxyribonucleic acid splicing or by proteolytic cleavage. This review focuses on new research into these mediators as potential biomarkers for vascular complications in diabetes.

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“…Interestingly, case/controls studies have revealed a strong link between an individual's possession of the − 374A allele or AA genotype and protection against vascular disease. These include decreased risk of cardio-and cerebral-vascular disease [106][107][108][109], a decrease in restenosis after angioplasty [110], the number of affected vessels [111,112], and mortality after myocardial infarction (Table 2) [113]. Studies have not identified an association with diabetic retinopathy [92,[114][115][116], which is not surprising since genetic studies of diabetic microvascular complications did not reveal a genetic component on the pathogenesis of retinopathy.…”

Section: Promoter Region Variants Of the Rage Gene: − 374t > Amentioning

confidence: 99%

RAGE: a novel biological and genetic marker for vascular disease

2009

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RAGE [receptor for AGEs (advanced glycation end-products)] plays an important role in the development and progression of vascular disease. Studies in cultured cells and small animal models of disease have clearly demonstrated that RAGE is central to the pathogenesis of vascular disease of the macro- and micro-vessels in both the diabetic and non-diabetic state. Emerging results from human clinical studies have revealed that levels of circulating soluble RAGE in the plasma may reflect the presence and/or extent of vascular disease state. Additionally, genetic variants of the RAGE gene (AGER in HUGO nomenclature) have been associated with vascular disease risk. Combining RAGE circulating protein levels and the presence of particular RAGE polymorphisms may be a useful clinical tool for the prediction of individuals at risk for vascular disease. Therapeutic intervention targeted at the RAGE gene may therefore be a useful means of treating pathologies of the vasculature.

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The −374A allele of the receptor for advanced glycation end products (RAGE) gene promoter is a protective factor against cardiovascular lesions in type 2 diabetes mellitus patients

Abstract: This result confirms that the -374AA genotype of the RAGE gene promoter is a protective factor against the severity of CAD lesions in type 2 diabetic patients.

Cited by 28 publications

References 21 publications

Genetic Predisposition to Advanced Glycation End Products Toxicity Is Related to Prognosis of Chronic Hemodialysis Patients

Genetic Predisposition to Advanced Glycation End Products Toxicity Is Related to Prognosis of Chronic Hemodialysis Patients

RAGE receptor and its soluble isoforms in diabetes mellitus complications

RAGE: a novel biological and genetic marker for vascular disease

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