Thesis Defense Announcement
To: The George Mason University Community
Candidate: Gladys Shaw
Program: M.S. in Biology
Date: Thursday May 11, 2017
Time: 12:00 Noon
Place: Krasnow Institute, room 229
George Mason University
“Gene Polymorphisms of the Receptor for Advanced Glycation End Products and Its Role in the AGE-RAGE Pathway and Inflammation”
Committee Chair: Dr. Ancha Baranova
Thesis Director: Dr. Aybike Birerdinc
Committee Member: Dr. Karl Fryxell
All are invited to attend the defense.
Advanced glycation end products (AGEs) are cross-linked, non-degradable aggregates of proteins, lipids and nucleic acids produced in the course of aging and many aging-associated chronic diseases. Additionally, the receptor for advanced glycation end products (RAGE) 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 aided by a) Varying levels of RAGE isoforms; b) Polymorphisms in AGER influencing ligand-receptor interaction or RAGE levels; c) Variations in concentration of RAGE’s ligand, advanced glycation end products (AGE). These variations will alter inflammatory milieu within the human body. TaqMan qPCR was employed in genotyping of 4 inflammation-related SNPs located within the AGER gene (Gly82Ser, G1704T, T-374A, and T-429C) in 340 obese patients. The mean age of the patients was 44 years and mean BMI was 46 kg/m2. About a third of the patients had type 2 diabetes (31.2%). Additionally, around a third have been diagnosed with NAFLD (30.6%) or NASH (30.3%) by histopathological analysis. ELISA assays were used in the analysis of RAGE protein isoforms in the serum of these patients. Statistical tests were used to determine whether a particular genotype/haplotype of the AGER locus produces significantly different levels of RAGE protein. Correlations between levels of circulating AGE and prevalence of NAFLD in those with specific AGER genotypes were detected. Our findings may explain why only a subset of NAFLD patients progresses to NASH.