Ozlem Kurnaz

Different effects of PPARA, PPARG and ApoE SNPs on serum lipids in patients with coronary heart disease based on the presence of diabetes

BACKGROUND The aim of this study was to investigate the individual or combined effects of PPARA-L162V, PPARG-C161T and APOE polymorphisms on hyperlipidemia in coronary heart disease (CHD) patients. METHODS Our study included 223 patients with CHD (103 with type 2 diabetes (T2DM), 120 without diabetes) and 101 controls. All genotypes were determined by PCR-RFLP technique. RESULTS Genotypic and allelic distributions of PPARA-L162V polymorphism were similar between study and control groups (p>0.05). The serum total-cholesterol (TC) and LDL-cholesterol (LDL-C) levels were higher in PPARA-V162 allele carriers in non-diabetic CHD patients (p=0.007 and p=0.038, respectively). The increasing effect of the PPARA-V162 allele on serum TC and LDL-C levels was weakened with the presence of PPARG-161T allele in the non-diabetic CHD patients. The ApoE4-PPARA-V162 allelic combination of the ApoE/PPARA genes was found to be more frequent in diabetic CHD patients independent of serum lipids (p=0.035). CONCLUSIONS The PPARA V162 allele has an increasing effect on TC and LDL-C levels and this effect was reduced by carrying PPARG T161 allele in non-diabetic CHD patients. On the other hand, the V162 allele may be associated with an increased risk of CHD in diabetic CHD patients due to the presence of ApoE4 allele independent of serum lipids. We suggest that the PPARA L162V polymorphism may have diverse effects on serum lipids and CHD risk depends on the presence of T2DM.

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

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 C27. 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.

The effects of age and gender on the relationship between HMGCR promoter-911 SNP (rs33761740) and serum lipids in patients with coronary heart disease.

BACKGROUND Hydroxymethylglutaryl-Coenzyme A Reductase (HMGCR) catalyzes the rate-limiting step of cholesterol biosynthesis. This enzyme is the target of the widely available cholesterol lowering statins. In this population-based case-control study, the frequencies of -911 C>A polymorphism (rs3761740) of the HMGCR gene in patients with coronary heart disease (CHD) and healthy subjects were investigated and the correlations between the different genotypes and hypercholesterolemia with cardiovascular risk factors were analyzed. METHODS The HMGCR genotypes were determined in 365 patients with CHD and 365 controls by PCR-RFLP assay. Anthropometric measurements were measured in all participants. RESULTS There was no significant difference in the genotype frequencies of the HMGCR polymorphism between the male subjects of both patient and control groups, however, the HMGCR-CC genotype was found to be more frequent in female patients with CHD than female controls (p=0.002). The HMGCR-CC genotype showed higher total-cholesterol (TC) and LDL-cholesterol (LDL-C) levels than the CA+AA genotypes in male CHD patients (p=0.018). Due to this significant sex interaction, a multivariate analysis was conducted on the patient group. In the multivariate logistic regression analysis, the HMGCR-CC genotype was significantly associated with age<55 (OR=2.837, p=0.001) and TC ≥ 5.18 mmol/L (OR=1.970, p=0.027) in male subjects. However, this association was not observed in female patients (p>0.05). This analysis confirmed that the HMGCR-CC genotype was associated with elevated TC levels in male CHD patients with age<55 years. CONCLUSION These results suggest that age and sex modify the contribution of the HMGCR-911 polymorphism to fasting serum TC, LDL-C levels and risk of CHD.

PPAR-Gamma Pro12Ala Polymorphism and Gastric Cancer Risk in a Turkish Population

BACKGROUND Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand dependent transcription factor involved in various processes, including carcinogenesis. We aimed to investigate any possible association of the PPARγPro12Ala (rs1801282) polymorphism with risk of developing gastric cancer (GC). PATIENTS AND METHODS A hospital based case control study was designed covering 50 patients with GC and 120 healthy controls. The frequencies of PPARγPro12Ala (rs1801282) were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS The Ala12 allele of the PPARγPro12Ala G gene was associated with a 1.95 fold increased risk of GC development (p: 0.022; 95% CI: 1.58-2.40). Subgroup analyses showed that the same allele was also associated with metastasis (p: 0.000; OR:4.09; 95%CI:2.273-7.368) and differentiation (p: 0.004; OR:1.95; 95%CI:1.335-2.875) in patients with GC. CONCLUSION This study suggests that the PPARγPro12Ala G (Ala12) allele might be associated with development, differentiation and metastatic process of GC in the Turkish population. Further studies conducted in larger study groups and in different ethnic populations will be needed to clarify the exact role of the PPARγPro12Ala polymorphism in GC.

The Association of MTHFR C677T Gene Variants and Lipid Profiles or Body Mass Index in Patients With Diabetic and Nondiabetic Coronary Heart Disease

The aim of this study is to investigate whether methylenetetrahydrofolate reductase (MTHFR) C677T mutation is associated with the development of hyperlipoproteinemia and obesity in coronary heart disease (CHD).