PPARgamma promoter polymorphisms and acute coronary syndrome.
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.
Evangelisti
L
L
Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence, University of Florence, Florence, Italy. lucia.evangelisti@gmail.com
Attanasio
M
M
Lucarini
L
L
Sofi
F
F
Marcucci
R
R
Giglioli
C
C
Valente
S
S
Gensini
Gf
G
Abbate
R
R
Pepe
G
G
D054058:Acute Coronary Syndrome / Q000175:diagnosis* / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047495:PPAR gamma / Q000378:metabolism*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
D047495:PPAR gamma