The RAGE G82S polymorphism is not associated with rheumatoid arthritis independently of HLA-DRB1*0401

Steenvoorden, M.M.C.; Mil, Annette H M van der Helm-van; Stoeken, G.; Bank, Ruud A.; DeVries, Rebecca; Huizinga, T.W.J.; DeGroot, Jeroen; Toes, René E. M.

doi:10.1093/rheumatology/kel011

Cited by 11 publications

(7 citation statements)

References 8 publications

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Section: Discussionsupporting

confidence: 91%

“…At least one RAGE allele was present as Ser82 in 10% to 20% of RA patients in the present prospective and retrospective cohorts, figures similar to previous studies of RA patients and higher than those in unselected population-based studies or control cohorts [18,19,21,40]. We confirm here that the RAGE Ser82 allele is in linkage disequilibrium with HLA–DRB1*0401 [40-42]. Because the RAGE Ser82 isoform is a functional polymorphism enhancing receptor signaling through MAP kinases and NF-κB, which activate an array of proinflammatory genes [18], we predicted an association of this polymorphism with CV events in RA, potentially through a more pronounced inflammatory response in these patients.…”

Section: Discussionsupporting

confidence: 90%

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Receptor for advanced glycation end products Glycine 82 Serine polymorphism and risk of cardiovascular events in rheumatoid arthritis

et al. 2007

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Patients with rheumatoid arthritis (RA) are at risk of excess mortality, predominantly owing to cardiovascular (CV) events. The receptor for advanced glycation end products (RAGE) has been implicated in the perpetuation of the chronic inflammatory response in vascular disease. A Gly82→Ser polymorphism in the RAGE gene, which is associated with enhanced RAGE signaling, is present more frequently in patients with RA than the general population. To investigate whether RAGE Gly82→Ser polymorphism is associated with CV events in RA, we examined CV events, CV risk factors, features of RA and RAGE Gly82→Ser polymorphism in 232 patients with RA attending a tertiary referral hospital. CV events, the duration and severity of RA, and risk factors for CV disease were determined using patient questionnaires, chart review, laboratory analysis and radiographs. DNA was typed for HLA–DRB1 genes and RAGE Gly82→Ser polymorphism. The RAGE Ser82 allele, which is in linkage disequilibrium with the RA susceptibility allele HLA–DRB1*0401, was carried by 20% of patients. More than 20% of the cohort had suffered a vascular event; a shorter duration of RA, but not the RAGE genotype, was significantly associated with CV events. However, a history of statin use was protective. Thus, the RAGE Ser82 allele, associated with enhanced RAGE signaling, does not predispose to CV events in RA. However, treatment of hyperlipidemia with statins reduces the probability of a CV event.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 90%

Receptor for advanced glycation end products Glycine 82 Serine polymorphism and risk of cardiovascular events in rheumatoid arthritis

et al. 2007

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“…A few studies have documented this point. A work on rheumatoid arthritis showed that G82S was associated with its disease independently of HLA DRB11 [127]. In type 1 diabetic patients, LD between AGER and HLA variants seemed to have a clinical correlation.…”

Section: Linkage Disequilibrium With Mhc Gene Variantsmentioning

confidence: 99%

Pathological Implications of Receptor for Advanced Glycation End-Product (AGER) Gene Polymorphism

et al. 2019

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The receptor for advanced glycation end-products (RAGE) is a cell surface transmembrane multiligand receptor, encoded by the AGER gene. RAGE presents many transcripts, is expressed mainly in the lung, and involves multiple pathways (such as NFκB, Akt, p38, and MAP kinases) that initiate and perpetuate an unfavorable proinflammatory state. Due to these numerous functional activities, RAGE is implicated in multiple diseases. AGER is a highly polymorphic gene, with polymorphisms or SNP (single-nucleotide polymorphism) that could be responsible or co-responsible for disease development. This review was designed to shed light on the pathological implications of AGER polymorphisms. Five polymorphisms are described: rs2070600, rs1800624, rs1800625, rs184003, and a 63 bp deletion. The rs2070600 SNP may be associated with the development of human autoimmune disease, diabetes complications, cancer, and lung diseases such as chronic obstructive pulmonary disease and acute respiratory distress syndrome. The rs1800624 SNP involves AGER gene regulation and may be related to reduced risk of heart disease, cancer, Crohn’s disease, and type 1 diabetes complications. The rs1800625 SNP may be associated with the development of diabetic retinopathy, cancer, and lupus but may be protective against cardiovascular risk. The rs184003 SNP seems related to coronary artery disease, breast cancer, and diabetes. The 63 bp deletion may be associated with reduced survival from heart diseases during diabetic nephropathy. Here, these potential associations between AGER polymorphisms and the development of diseases are discussed, as there have been conflicting findings on the pathological impact of AGER SNPs in the literature. These contradictory results might be explained by distinct AGER SNP frequencies depending on ethnicity.

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“…In contrast, Finnish (Pulkkinen et al. , 2000), Dutch (Steenvoorden et al. , 2006) and North American (Hofmann et al.…”

Section: Resultsmentioning

confidence: 97%

Polymorphisms of the promoter and exon 3 of the receptor for advanced glycation end products (RAGE) in Euro‐ and Afro‐Brazilians

Torres

Beltrame

Santos

et al. 2011

Int J Immunogenetics

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The receptor for advanced glycation end products (RAGE or AGER), a member of the immunoglobulin superfamily, is involved in pathologies such as atherosclerosis and diabetes. Over 50 SNPs were reported for RAGE, among which were the promoter region polymorphisms -429T>C (rs1800625), -374T>A (rs1800624) and a 63-bp deletion (-407 to -345 bp), all related to increased RAGE expression. Additionally, in the exon 3, a putative site of binding ligands, the missense variation G82S (rs2070600) was associated with skin disorders in patients with diabetes. We have determined allele, genotype and haplotype frequencies of RAGE polymorphisms -429T>C, -374T>A, 63-bp deletion and G82S in Euro-Brazilians (n = 108) and Afro-Brazilians (n = 91), characterized according to the predominant ancestry of the individuals. The allele frequencies for Euro- and Afro-Brazilians were as follows: -429C, 12.5% vs. 12.1% (P = 0.90); -374A, 31.5% vs. 26.2% (P = 0.25); 63del, 0.0% vs. 3.8% (P = 0.004); and 82S, 1.9% vs. 0.6% (P = 0.24). Absolute linkage disequilibrium was found between the promoter polymorphisms -429T>C and -374T>A plus the 63-bp deletion (D'=1.000; P < 0.0001). The haplotype frequencies differed (P = 0.003) between Euro- and Afro-Brazilians. Our results showed that the frequencies of the 63-bp deletion were higher in Afro-Brazilians, while the other analysed polymorphisms were similarly distributed in the studied populations. The -374T>A plus 63-bp deletion polymorphism captures more than 80% of the haplotypic variation in the studied population.

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The RAGE G82S polymorphism is not associated with rheumatoid arthritis independently of HLA-DRB1*0401

Cited by 11 publications

References 8 publications

Receptor for advanced glycation end products Glycine 82 Serine polymorphism and risk of cardiovascular events in rheumatoid arthritis

Receptor for advanced glycation end products Glycine 82 Serine polymorphism and risk of cardiovascular events in rheumatoid arthritis

Pathological Implications of Receptor for Advanced Glycation End-Product (AGER) Gene Polymorphism

Polymorphisms of the promoter and exon 3 of the receptor for advanced glycation end products (RAGE) in Euro‐ and Afro‐Brazilians

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