Synergistic effect between polymorphisms of PPARA and ABCA1 genes on the premature coronary artery disease.
OBJECTIVE
Progression of atherosclerosis, the main reason of cardiovascular diseases, depends on multiple genetic and environmental factors. Polymorphic variants of genes involved in the lipids metabolism may genetically differentiate human populations and determine a susceptibility to the disease. The aim of the present study was to evaluate a possible interaction between R219K polymorphism of ABCA1 gene and G > C polymorphism in intron 7 of PPARA gene in determining the risk of the CAD.


METHODS
We studied 358 subjects: 178 patients with angiographically confirmed CAD and 180 blood donors without history of CAD. Polymorphisms were genotyped using the PCR-RFLP method.


RESULTS
In spite of a small or no correlation between single polymorphism and CAD we observed that the frequencies of AA + GC,CC genotype pattern (ABCA1 and PPARA gene) were significantly higher in CAD group than in controls. OR values were especially high in multiple logistic regression and were higher for male subgroups. The synergy index value equals 3.98 and indicates a quite strong synergistic effect between the analysed polymorphisms. We also observed that C allele carriers of PPARA gene had a significantly lower total and LDL-cholesterol level.


CONCLUSIONS
The present study shows that R219K polymorphism of ABCA1 gene and G > C polymorphism in intron 7 of PPARA gene act cumulatively and synergistically in determining the risk of premature CAD.
Balcerzyk
Anna
A
Department of Biochemistry and Medical Genetics, Medical University of Silesia, Katowice, Poland. biogen@slam.katowice.pl
Zak
Iwona
I
Krauze
Jolanta
J
D000293:Adolescent; D000328:Adult; D000483:Alleles; D053302:Apolipoprotein C-I / Q000235:genetics*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007438:Introns; D016015:Logistic Models; D008875:Middle Aged; D047493:PPAR alpha / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors
D053302:Apolipoprotein C-I; D047493:PPAR alpha