GENETIC ANALYSIS OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS-GAMMA (PPARG) PROMOTERS: ACUTE CORONARY SYNDROME PATIENTS VERSUS CONTROLS
Abstract number: P-S-453
Evangelisti1 L., Attanasio2 M., Sofi2 F., Pepe2 G., Marcucci2 R., Fatini2 C., Valente2 S., Giglioli2 C., Abbate2 R., Gensini3 G.F.
11Department of Medical and Surgical Critical Care, University of Florence, Italy, florence 22Department of Medical and Surgical Critical Care, University of Florence, Italy 33Department of Medical and Surgical Critical Care, Centro S.Maria degli Ulivi, Fondazione Don Carlo Gnocchi, Onlus,IRCSS, Florence, Italy, Italy
How-to-cite Evangelisti L, Attanasio M, Sofi F, Pepe G, Marcucci R, Fatini C, Valente S, Giglioli C, Abbate R, Gensini GF. GENETIC ANALYSIS OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS-GAMMA (PPARG) PROMOTERS: ACUTE CORONARY SYNDROME PATIENTS VERSUS CONTROLS. J Thromb Haemost 2007; 5 Supplement 2: P-S-453
Abstract
Introduction: PPARg is a nuclear transcription factor involved in the control of energy, lipid and glucose homeostasis. The gene is located on chromosome 3 (3p25) and produces 4 different PPARg mRNAs by alternative splicing and promoter (Pr) usage. PPARg may act directly on local vasculature in several aspects of atherothrombosis (lipid metabolism, foam cell responses, inflammation), suggesting that it may be an important determinant of gene expression during atherogenesis and it is a potential candidate gene for acute coronary syndrome (ACS). The aim of the study was: 1) to look for new genetic variations in PPARg Pr, 2) to investigate PPARg Pr polymorphisms association with ACS.
Methods: We studied 202 patients affected by ACS, (median age 66 ys,145 males) compared with age- and sex- matched control group (n=295). The genetic variants were evaluated using heteroduplex analysis on dHPLC and direct sequencing or RFLP analysis.
Results: We identified in PPARg promoters 3 new variants: T65597C, C25924T, T93640C and 4 already published polymorphisms: C25819G, T26233A, T93673C, C93695T. the C93695T (Pr 4) mutation showed a significantly different distribution between control and ACS populations (genotype distribution and allele frequency: p<0.001). The rare allele T of Pr4 (C93695T) conferred a significant protection against ACS at both univariate (O.R.:0.45,95%C.I.:0.29-0.69, p<0.001) and multivariate analysis adjusted for sex, age and traditional cardiovascular risk factors (O.R.:0.44,95%C.I.:0.25-0.76, p<0.005)
Conclusions: These results suggest a new role for PPARg polymorphism C93695T in ACS. Further investigations in order to understand the role of PPARg promoters polymorphisms in the regulation of atherosclerosis process are needed.
