BACKGROUND: Atherosclerosis is the most important cause of coronary artery disease (CAD). Genetic predisposition to CAD is related to polymorphisms of genes encoding products functionally involved in pathogenesis of atherosclerosis. Polymorphisms of genes participating in monocyte adhesion and diapedesis, lipid metabolism and fibrinolysis regulation may be partially responsible for this process. The aim of our study was to assess the polymorphic variants frequencies of ICAM1, APOE, PPARA and PAI-1 genes in CAD patients and healthy blood donors and to find specific arrangement of polymorphic variants which would differentiate both groups. METHODS: We studied 146 CAD patients and 121 healthy blood donors. Polymorphisms in analyzed genes were examined using PCR-RFLP analysis. RESULTS: We found significantly higher frequency of 5G allele of PAI-1 gene in patients than in control subjects (p = 0.038, OR = 1.44). We observed also a considerably higher frequency of contemporaneous carriers of two or three "proatherosclerotic" variants: 1) PPARA and PAI-1, 2) APOE and ICAM1 and 3) PPARA, ICAM1 and PAI-1 in CAD group comparing to control subjects. The number of "proatherosclerotic" variants carriers differentiate studied groups also independently of specific genotype arrangement. CONCLUSION: In conclusion, contemporaneous carrier-state of two or three polymorphic variants within analyzed genes is associated with CAD.
BACKGROUND:Atherosclerosis is the most important cause of coronary artery disease (CAD). Genetic predisposition to CAD is related to polymorphisms of genes encoding products functionally involved in pathogenesis of atherosclerosis. Polymorphisms of genes participating in monocyte adhesion and diapedesis, lipid metabolism and fibrinolysis regulation may be partially responsible for this process. The aim of our study was to assess the polymorphic variants frequencies of ICAM1, APOE, PPARA and PAI-1 genes in CAD patients and healthy blood donors and to find specific arrangement of polymorphic variants which would differentiate both groups. METHODS: We studied 146 CAD patients and 121 healthy blood donors. Polymorphisms in analyzed genes were examined using PCR-RFLP analysis. RESULTS: We found significantly higher frequency of 5G allele of PAI-1 gene in patients than in control subjects (p = 0.038, OR = 1.44). We observed also a considerably higher frequency of contemporaneous carriers of two or three "proatherosclerotic" variants: 1) PPARA and PAI-1, 2) APOE and ICAM1 and 3) PPARA, ICAM1 and PAI-1 in CAD group comparing to control subjects. The number of "proatherosclerotic" variants carriers differentiate studied groups also independently of specific genotype arrangement. CONCLUSION: In conclusion, contemporaneous carrier-state of two or three polymorphic variants within analyzed genes is associated with CAD.
Authors: Sharon Cresci; Philip G Jones; Carmen C Sucharov; Sharon Marsh; David E Lanfear; Adam Garsa; Michael Courtois; Carla J Weinheimer; Jun Wu; Michael A Province; Daniel P Kelly; Howard L McLeod; John A Spertus Journal: Pharmacogenomics Date: 2008-10 Impact factor: 2.533