Short Communication The functional polymorphisms -429T>C and -374T>A of the RAGE gene promoter are not associated with gestational diabetes in Euro-Brazilians

Abstract

ABSTRACT. The receptor for advanced glycation end products (RAGE or AGER) is a multiligand member of the immunoglobulin superfamily. RAGE is expressed in several tissues, including human myometrium, chorionic villi and placenta. Advanced glycation end products are the best studied ligands of RAGE; they have proinflammatory actions in human gestational tissues, increasing oxidative stress and the release of cytokines and prostaglandins. We RAGE SNPs and gestational diabetes investigated the association of RAGE gene promoter polymorphisms -429T>C (rs1800625) and -374T>A (rs1800624) with gestational diabetes. A sample of 750 unrelated European origin pregnant Brazilian women were classified as nondiabetic (control group, N = 600) or having gestational diabetes (N = 150) according to American Diabetes Association 2009 criteria. Genotyping was performed by PCR-RFLP. The frequencies of the rare alleles -429C (6.3 versus 9.1%) and -374A (26 versus 30%) were not significantly different between the gestational diabetes patients and healthy pregnant women. Also, the -429T>C and -374T>A polymorphisms were not associated with body mass index, lipid profile, fasting glycemia, HbA1C, or insulin requirement. We found that functional promoter polymorphisms of the RAGE gene were not associated with gestational diabetes or its complications in these Euro-Brazilian patients.

Low prevalence of glucokinase gene mutations in gestational diabetic patients with good glycemic control

“…Clinical characteristics and biochemical parameters (Table 2) of the studied groups were similar to those reported in other studies (Santos et al, 2010a). GDM patients were usually heavier since overweight is a risk factor associated with this pathology and type 2 diabetes (Rosenberg et al, 2005;Rivero et al, 2008).…”

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

“…The rs1800624 SNP is associated with a threefold increase in AGER expression in vitro , including sRAGE expression. sRAGE serves as an endogenous antagonist by neutralizing proinflammatory ligands that are in turn unable to activate inflammatory pathways [85]. Absolute or strong linkage disequilibrium, depending on the studies, was found between promoter polymorphisms: rs1800625 (−429T>C), rs1800624 (−374T>A), and a 63 bp deletion [29].…”

“…A protective effect of rs1800624 against diabetic retinopathy in type 2 diabetic patients was identified in a meta-analysis [42]. On the other hand, a study on Caucasian Brazilians with type 2 diabetes did not find any association between the presence of the A allele and diabetic retinopathy, diabetic nephropathy, or ischemic heart disease [93], while other reports did not find any association between rs1800264 and cardiovascular diseases or diabetes [85]. No association was found between rs1800264 and the presence of heart failure in unselected patients and between rs1800264 and higher mortality in those with heart failure [94].…”

“…It involves an increase in RAGE expression, which might influence the pathogenesis of inflammatory diseases [14, 32, 83, 106, 107]. The level of increased expression of RAGE is around twofold in vitro [85]. There is a higher expression of sRAGE and esRAGE in the presence of rs1800625 [18].…”

HFE Gene Mutation Associated with the Severity of Gestational Diabetes Mellitus in Belarusian Women

“…Number of human genes was investigated dealing with GDM: HLA, SUR1 (sufonylurea receptor gene), GCK (glucokinase gene), TCF7L2 (transcription factor 7-like 2 gene), HFE (hemochromatosis gene) and others with contradicting results [5][6][7][8][9][10].…”