The −374T/A RAGE Polymorphism Protects Against Future Cardiac Events in Nondiabetic Patients with Coronary Artery Disease

Falcone, Colomba; Geroldi, Diego; Buzzi, Maria Paola; Emanuele, Enzo; Yılmaz, Yusuf; Fontana, Jacopo Maria; Vignali, Luigi; Boiocchi, Chiara; Sbarsi, Ilaria; Cuccia, Mariaclara

doi:10.1016/j.arcmed.2007.11.003

Cited by 38 publications

(25 citation statements)

References 19 publications

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“…RAGE has not been studied before in CFS patients. Our data would seem to indicate a lack of direct involvement of AGEs as ligands as it occurs during the inflammation involved in atherosclerosis (4,(28)(29). Interestingly, no linkage disequilibrium was observed in CFS between RAGE and the close DRB 1 genes which, conversely, was found in controls.…”

Section: Discussionmentioning

confidence: 64%

Molecular Study of Receptor for Advanced Glycation Endproduct Gene Promoter and Identification of Specific HLA Haplotypes Possibly Involved in Chronic Fatigue Syndrome

Carlo-Stella

Beigrezaei

Silvestri

et al. 2009

Int J Immunopathol Pharmacol

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The receptor for advanced glycation end product (RAGE) is thought to play an important role in inflammation. Chronic Fatigue Syndrome (CFS) is a long-lasting fatigue that compromises at least 50% of a subject's daily activities without other known cause. Immune dysfunction has been implicated and an association with a peculiar genetic cytokine profile, predisposing to an immunomodulatory response of inflammatory nature, was found. The aim of this study is to analyse RAGE polymorphisms and HLA-DRB1 alleles in seventy-five Italian CFS patients and 141 controls matched for age, sex and ethnicity. These two groups underwent genomic study for RAGE –374T/A and –429C/T promoter polymorphisms; moreover, 46 patients and 186 controls were typed for HLA-DRB1 at low resolution molecular level. Of these, 31 patients and 99 controls also underwent “high resolution analysis” to define the HLA-DRB1*11 and DRB1*13 alleles. The haplotypes RAGE-374T, DRB1*04; RAGE-374T, DRB1*09; RAGE-374T, DRB1*11; RAGE-374A, DRB1*13; RAGE-429T, DRB1*04 and RAGE-429C, DRB1*11 were significantly more frequent in CFS patients, whereas RAGE-429C, DRB1*07 would seem protective. A significantly lower frequency of DRB1*1104 (5.4% vs 12.9% p=0.04, OR=0.39) and a significantly higher frequency of HLA-DRB1*1301 (13.0% vs 5.1% p=0.006, OR= 2.79) were found in CFS patients. A synergic effect was observed with RAGE polymorphism. The OR values strengthened in the following cis combinations: RAGE-374A, HLA-DRB1*1104 (OR=0.27) and RAGE-374A, HLA-DRB1*1301 (OR=6.23). HLA haplotypes rather than single alleles of RAGE or of DRB1 genes seem to be involved in CFS, probably including a subregion of major interest.

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Section: Discussionmentioning

confidence: 64%

Molecular Study of Receptor for Advanced Glycation Endproduct Gene Promoter and Identification of Specific HLA Haplotypes Possibly Involved in Chronic Fatigue Syndrome

Carlo-Stella

Beigrezaei

Silvestri

et al. 2009

Int J Immunopathol Pharmacol

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“…Falcone et al [16,68] Association with increased risk of ischemic stroke Zee et al [66] Association with proteinuria and CVD in type 1 diabetes…”

Section: From Biomarkers To Target Therapymentioning

confidence: 98%

Soluble forms of RAGE in internal medicine

et al. 2009

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The receptor for advanced glycation end-products (RAGE) and its ligands are intimately involved in the pathobiology of a wide range of diseases that share common features, such as enhanced oxidative stress, immune/inflammatory responses, and altered cell functions. Soluble forms of RAGE (sRAGE), including the splice variant endogenous secretory (es)RAGE, have been found circulating in plasma and tissues. Experimental data suggest that these isoforms may neutralize the ligand-mediated damage by acting as a decoy. Moreover, evidence is mounting to support a role for both sRAGE and esRAGE as biomarkers or endogenous protection factors against RAGE-mediated pathogenesis. In this review, we will focus on clinical and therapeutical implications arising from studies investigating the significance of soluble RAGE isoforms in several clinical settings, including cardiovascular disease, diabetes mellitus, hypercholesterolemia, chronic renal failure, immune/inflammatory diseases, pulmonary diseases, neurodegeneration, and cancer.

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“…It is a complex condition resulting from numerous gene interactions, and various genes have previously been studied (22)(23)(24). Inflammation was recently proven to be associated with the pathogenesis of atherosclerosis and its complications (25).…”

Section: Discussionmentioning

confidence: 99%

CR1 genotype and haplotype involvement in coronary artery disease: The pivotal role of hypertension and dyslipidemia

et al. 2009

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Abstract. Inflammation plays a pivotal role in the pathogenesis of atherosclerosis and coronary syndromes. Atherosclerosis is a complex multifactorial disorder. Data indicate that the complement proteins play a crucial role in the link between inflammation and atherogenesis. Thus, there is evidence supporting the role of complement activation in atherogenesis. Complement receptor 1 (CR1) is a membrane protein found on different cells involved in various activities of the complement system. We demonstrated the possible involvement of CR1 in atherosclerosis studying the allele and genotype frequencies of the CR1 Pro1827Arg, CR1 His1208Arg exon 22 and int27 HindIII polymorphisms in a sample of patients with angiographically documented coronary artery disease (CAD) (n=550) and in healthy controls (n=380) matched for age, gender and ethnicity. Our data showed no significant deviations between the two groups with regard to either allele or genotype frequencies. After stratification according to risk factors, our analysis revealed a reduced frequency of the GG genotype of the Pro1827Arg polymorphism in patients with CAD and dyslipidemia vs the controls (p=0.031) and of the GG and LL genotypes in CAD patients with dyslipidemia vs CAD patients without dyslipidemia regarding the Pro1827Arg and CR1 HindIII intron 27 polymorphisms (GG, p=0.019; LL, p=0,184). We analyzed the haplotype frequencies of CR1. A decrease in CAD patients carrying the CAC haplotype compared to controls (p=0.043) and a decrease in the CAC haplotype in CAD patients with hypertension vs healthy controls (p=0,029) were demonstrated.Our data showed a possible involvement of CR1 gene polymorphisms in the predisposition to the development of this disease.

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The −374T/A RAGE Polymorphism Protects Against Future Cardiac Events in Nondiabetic Patients with Coronary Artery Disease

Cited by 38 publications

References 19 publications

Molecular Study of Receptor for Advanced Glycation Endproduct Gene Promoter and Identification of Specific HLA Haplotypes Possibly Involved in Chronic Fatigue Syndrome

Molecular Study of Receptor for Advanced Glycation Endproduct Gene Promoter and Identification of Specific HLA Haplotypes Possibly Involved in Chronic Fatigue Syndrome

Soluble forms of RAGE in internal medicine

CR1 genotype and haplotype involvement in coronary artery disease: The pivotal role of hypertension and dyslipidemia

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