Investigation of Polymorphic Variants of PPARD and APOE Genes in Turkish Coronary Heart Disease Patients

Abstract

The aim of this study was to determine the role of polymorphic variants of apolipoprotein E (APOE) and peroxisome proliferator-activated receptor delta (PPARD) genes in the development of coronary heart disease (CHD), and the PPARD and APOE gene-gene interaction in a Turkish population. This study was carried out using a sample of 223 patients with CHD (103 with diabetes and 120 without diabetes) and 101 controls. PPARD + 294T/C and APOE genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism technique. The PPARD and APOE genotype distributions were the same between study groups (p > 0.05). In the nondiabetic CHD patients, the PPARD + 294 C allele showed higher serum low-density lipoprotein cholesterol (LDL-C) level than the common + 294 TT homozygote genotype (3.83 +/- 1.01 vs. 3.33 +/- 1.14, p = 0.015). In addition, a significant association between APOE 4 and PPARD + 294 C alleles was detected based on their effects on LDL-C in the nondiabetic CHD patients (+ 294 C/APOE4: 4.43 +/- 0.88 vs. + 294 TT/nonAPOE 4: 3.48 +/- 1.09, p = 0.009). This association indicated the interaction of two genes on plasma LDL-C levels ascended in the order + 294 T< + 294 T-APOE 4< + 294 C< APOE 4< + 294 C-APOE 4. The PPARD + 294 C allele was associated with higher incidence of left ventricular hypertrophy (LVH) in all male patients with body mass index > 27. In addition, the CHD patients who were + 294 C allele carriers had a 2.48-fold higher risk of LVH than subjects homozygous for the T allele. An increasing effect of the PPARD + 294 C allele was shown on serum LDL-C levels in nondiabetic CHD patients. In addition, the results suggested that the + 294 C allele might be associated with an increased LVH risk especially in male CHD patients. Furthermore, gene-gene interaction between the PPARD + 294T/C and the APOE polymorphisms was observed regarding LDL-C concentrations.