PPARgamma Promoter Polymorphisms and Acute Coronary Syndrome
Received 1 July 2008; received in revised form 22 October 2008; accepted 9 November 2008. published online 31 December 2008.
Abstract
Background
PPARgamma (PPARg) is a nuclear transcription factor involved in the control of lipid and glucose homeostasis. Two PPARg common polymorphisms, Pro12Ala and 161C>T, have been found to be associated with cardiovascular disease. In this study, in addition to PPARg coding region, we looked for genetic variations in promoters and their association with acute coronary syndrome (ACS).
Methods
We studied 202 Italian patients with ACS, and 295 healthy Italian subjects by dHPLC (denaturing high-performance liquid chromatography), heteroduplex analysis and direct sequencing or RFLP (restriction fragment length polymorphism) analysis for screening mutations.
Results
We identified 7 new and 2 already published polymorphisms in PPARg promoters. The C>T93695 (promoter 4) mutation showed significantly different genotype distribution and allele frequency between controls and ACS patients (p<0.001); the T allele conferred a protection against ACS at both univariate (OR: 0.45, 95% CI 0.29–0.69: p<0.001) and multivariate analysis adjusted for sex, age and traditional cardiovascular risk factors (OR: 0.44, 95% CI 0.25–0.76: p<0.005). Moreover, the 161C>T polymorphism allele frequency (p=0.03) and genotype distribution (p=0.015) resulted to be different in ACS group if compared to healthy controls.
Conclusions
The protective role of 93695C>T polymorphism in PPARg promoter in ACS suggests that PPARg genetic variants may affect the susceptibility to atherosclerotic diseases.
aDepartment of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence, Center of the Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Disease to Develop Novel Therapies, University of Florence, Italy
bDepartment of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Italy
cCentro S. Maria agli Ulivi, Fondazione Don Carlo Gnocchi, Onlus, IRCCS, Florence, Italy
Corresponding author at: Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence, Viale Morgagni 85, 50134 Florence, Italy. Tel.: +39 055 7949420; fax: +39 055 7949418.
ABSTRACT