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RAGE is a multi-ligand transmembrane glycoprotein that promotes biological signals associated with inflammatory responses and degenerative diseases. sRAGE is a soluble variant that has been proposed as an inhibitor of RAGE activity. The −374 T/A and −429 T/C polymorphisms of the advanced glycation end-product receptor AGER gene have been associated with the development of some diseases, such as types of cancer, cardiovascular disease, and micro- and macro-vascular disease in diabetes, among others, but their role in metabolic syndrome (MS) is still unknown. We studied 80 healthy males without MS, and 80 males with MS, according to the harmonized criteria. The −374 T/A and −429 T/C polymorphisms were genotyped by RT-PCR, and sRAGE was measured by ELISA. Allelic and genotypic frequencies did not differ between the non-MS and MS groups (−374 T/A p = 0.48, p = 0.57 and −429 T/C p = 0.36, p = 0.59, respectively). Significant differences were found in fasting glucose levels and diastolic blood pressure in the genotypes of the −374 T/A polymorphism in the non-MS group (p < 0.01 and p = 0.008). Glucose levels were different in the −429 T/C genotypes in the MS group (p = 0.02). The sRAGE levels were similar in both groups, but the non-MS group showed a significant difference between individuals with only 1 or 2 components of metabolic syndrome (p = 0.047). However, no associations of any SNP with MS were found (recessive model p = 0.48, dominant model p = 0.82 for −374 T/A; recessive model p = 0.48, dominant model p = 0.42 for −429 T/C). The −374 T/A and −429 T/C polymorphisms were not associated with MS in a Mexican population and had no influence on serum sRAGE levels.

RAGE is a multi-ligand transmembrane glycoprotein that promotes biological signals associated with inflammatory responses and degenerative diseases. sRAGE is a soluble variant that has been proposed as an inhibitor of RAGE activity. The −374 T/A and −429 T/C polymorphisms of the advanced glycation end-product receptor AGER gene have been associated with the development of some diseases, such as types of cancer, cardiovascular disease, and micro- and macro-vascular disease in diabetes, among others, but their role in metabolic syndrome (MS) is still unknown. We studied 80 healthy males without MS, and 80 males with MS, according to the harmonized criteria. The −374 T/A and −429 T/C polymorphisms were genotyped by RT-PCR, and sRAGE was measured by ELISA. Allelic and genotypic frequencies did not differ between the non-MS and MS groups (−374 T/A p = 0.48, p = 0.57 and −429 T/C p = 0.36, p = 0.59, respectively). Significant differences were found in fasting glucose levels and diastolic blood pressure in the genotypes of the −374 T/A polymorphism in the non-MS group (p < 0.01 and p = 0.008). Glucose levels were different in the −429 T/C genotypes in the MS group (p = 0.02). The sRAGE levels were similar in both groups, but the non-MS group showed a significant difference between individuals with only 1 or 2 components of metabolic syndrome (p = 0.047). However, no associations of any SNP with MS were found (recessive model p = 0.48, dominant model p = 0.82 for −374 T/A; recessive model p = 0.48, dominant model p = 0.42 for −429 T/C). The −374 T/A and −429 T/C polymorphisms were not associated with MS in a Mexican population and had no influence on serum sRAGE levels.

Background. RAGE, a multi-ligand type 1 transmembrane glycoprotein belonging to the immunoglobulin superfamily, transduces biological signals associated with chronic cellular stress related with inflammatory responses, tissue damage, chronic and degenerative diseases (1). sRAGE is a variant of RAGE derived from cell surface cleavage mechanisms that could potentially act as endogenous inhibitors of RAGE activity (2). RAGE gene is highly polymorphic, with polymorphisms that could be responsible for disease development, like -374T/A (rs1800624) and -429T/C (rs1800625) polymorphisms. These are located in the promoter region and have marked effect on transcriptional activity. However, there have been conflicting findings between the potential association of RAGE polymorphisms and the development of diseases. In this work, we evaluated -374T/A (rs1800624) and -429T/C (rs1800625) polymorphisms and measured serum sRAGE levels in Mexican population with MS. Methods. A group of healthy men without any component of the MS (n=80), and a group of men with the MS (n=80) according to the harmonized criteria for the MS were included in this study. Blood genomic DNA was isolated and genotyped by RT-PCR for the -374T/A and -429T/C polymorphisms of RAGE gene. sRAGE in serum was measured with an ELISA kit. Results. The studied population complied with the Hardy-Weinberg equilibrium (p=0.58 for -374T/A, and p=0.79 for -429T/C). Differences were observed in all the components of the MS between the two groups (MS vs. healthy subjects, p<0.000). However, there were no differences in the population according to their genotype for the -374T/A (p=0.57) and -429T/C (p=0.59) polymorphisms. There was no difference in glucose (p=0.22), triglycerides (p=0.99), and cHDL (p=0.88) levels, or waist circumference (p=0.84) according to the genotype for the -374T/A polymorphism. The same was observed for the -429T/C polymorphism (glucose p=0.57, triglycerides p=0.69, cHDL p=0.77, waist circumference p=0.99). No association of MS with the -374T/A nor 429T/C polymorphism was found. There were no differences between groups in circulating sRAGE levels (p=0.132). Conclusion. According to our results, the -374T/A and -429T/C polymorphisms of RAGE gene are not associated with the MS in Mexican population, and have no influence on serum sRAGE levels. Some other factors could be playing a role for the high prevalence of the MS, such as eating habits. Gender should be taken into consideration, for our study was performed in men exclusively. References. (1) Serveaux-Dancer M et al., Dis Markers. 2019 Feb 4;2019:2067353. (2) Schmidt AM. Vascul Pharmacol. 2015 Sep;72:1-8.