GENE VARIANTS OF THE AGER PROTEIN IN INFLAMMATORY METABOLIC DISEASE

Background: Advanced glycation end products (AGEs) are cross-linked, non-degradable aggregates of proteins, lipids and nucleic acids produced in the course of ageing and many aging-associated chronic diseases. Additionally, the receptor for advanced glycation end products (AGER) is an important player in the pro-inflammatory pathway. Clinically, inflammatory metabolic diseases, such as diabetes, non-alcoholic fatty liver disease (NAFLD), and obesity, may be caused by a) varying levels of AGER isoforms; b) Polymorphisms in AGER influencing ligand-receptor interaction or AGER levels; c) Variations in concentration of AGER’s ligand, advanced glycation end products (AGE). These variations will alter inflammatory milieu. Methods: TaqMan qPCR was employed in genotyping 4 inflammation-related SNPs located within the RAGE gene (Gly82Ser, G1704T, T-374A, and T-429C). Furthermore, ELISA assays were used in the analysis of AGER protein isoforms in the serum of 342 obese patients. Statistical tests were used to determine whether a particular genotype/haplotype of the AGER locus produces significantly different levels of AGER protein. Data analysis will be carried out to determine the association of these polymorphisms and secreted levels of the AGER protein in metabolic disease. Results: The sample population in this study is drawn from patients at Inova Health System who have undergone bariatric surgery and have consented to the pertaining IRB approved protocols. The mean age of this population is 44 years and mean BMI is 46.06 kg/m². About a third of the patients have diabetes mellitus (31.2%). Additionally, around a third have been diagnosed with NAFLD (30.6%) or NASH (30.3%) via histopathological analysis. The qPCR results conform to Hardy-Weinberg equilibrium for all SNPs analyzed. Levels of circulating AGEs in patient serum average 6.88ug/mL in samples analyzed. Conclusion: Results of this ongoing study show potential for a correlation between levels of circulating AGE and prevalence of NAFLD in those with specific genotypes. Further statistical analysis, as well as increasing the sample size for ELISA testing will be completed and added to the dataset for a comprehensive analysis of these interactions.