Abstract

Identifying Potential Markers for Coronary Artery Disease using Quantitative Proteomics Approach

Shantanu Sengupta, Principal Scientist, IGIB

Maternal vitamin B12 deficiency has been shown to predict the onset of complex disorders like atherosclerosis, type II diabetes etc. in the next generation during their adulthood. In a country like India where a significant proportion of the population strictly adhered to vegetarian diet which is deficient in vitamin B12 is at risk of several physiological perturbations. We have previously shown that vitamin B12 deficiency is associated with coronary artery disease (CAD) in a north Indian population. In this context it is pertinent to understand the effect of maternal vitamin B12 deficiency in the next generation. To probe this using animal model system we have already shown that pups born to female rats fed with vitamin B12 deficient diet were obese and developed high levels of other intermediate traits such as triglycerides, cholesterol etc. Relative quantitation using 2D-DIGE followed by MALDI TOF/TOF analysis led to the identification of several differentially expressed proteins in liver of pups born to mothers fed vitamin B12 deficient diet vis-à-vis control diet. Our study thus provides the first evidence that maternal vitamin B12 deficiency influences lipid and other micronutrient metabolism in pups through regulation of PPAR signaling pathway. Further, we identified potential biomarkers for CAD using a plasma proteomics approach. Blood plasma from stable CAD and controls were subjected to iTRAQ based quantitative LC-MS proteomics. After multivariate logistic regression analysis adjusting for confounding factors we fond that a panel of 4 proteins (Apo A1,ApoA4,Apo C1 and albumin) along with diabetes and hypertension could account for about 88% of the CAD cases.