The Role of PPAR-gamma C161T Polymorphism in Colorectal Cancer Susceptibility.

BACKGROUND/AIM: This study aimed to determine the role of the peroxisome proliferator-activated receptor-gamma (PPARg) C161T genotype and allele frequencies in predisposition to colorectal cancer (CRC). PATIENTS AND METHODS: PPARg C161T (His447His; rs3856806) gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism analysis in patients with CRC (n=101) and controls (n=238). RESULTS: The T161 allele (CT+TT genotypes) of PPARg C161T polymorphism was associated with CRC development (p<0.001; OR=3.239, 95%CI=1.997-5.252). Subgroup analysis showed that the T161 allele was associated with a 3.056-fold increased risk for colon cancer (CC) (p<0.001; 95%CI=1.709-5.464) and 3.529-fold increased risk for rectal cancer (RC) (p<0.001; 95%C=1.784-6.981). Frequencies of the T161 allele were also higher in total CRC and CC patients with poorly differentiated tumors (p<0.001, c2=30,601, OR=3.109; 95%CI=1.970-4.906 and p<0.001, Fisher exact test, respectively). CONCLUSION: PPARg T161 allele carriers have increased risk for developing CRC.

Peroxisome Proliferator-Activated Receptor Gamma Pro12Ala/C161T Genotypes and Risky Haplotype Altering Risk of Breast Cancer: A Turkish Case-Control Study.

Breast cancer (BC) has a high incidence rate among women worldwide, and the mechanisms and etiology of this disease are not yet fully understood. The peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear hormone receptor that plays important roles in energy metabolism and cellular differentiation, is also suggested to be effective in cancer development. However, the results of studies investigating the cancer association with PPARgamma are inconsistent, creating a need for further investigation of the effects of this transcription factor on BC risk. We have examined the Pro12Ala-(rs1801282) and C161T-(rs3856806) polymorphisms of the PPARgamma gene in Turkish patients with BC in this case-control study. A total of 95 women diagnosed with BC as cases and 119 controls were genotyped for PPARgamma polymorphisms by polymerase chain reaction and restriction fragment length polymorphism techniques. The ProPro genotype and T161 allele were associated with an increased risk of BC comparing with the Ala12 allele and CC161 genotype, respectively (p < 0.001). The multivariate regression analysis confirmed that the ProPro genotype (p < 0.011), T161 allele (p < 0.001), smoking (p = 0.019), and advanced age (> 60 years) (p = 0.007) are risk factors for breast cancer. We also found that the PPARgamma Pro12Ala and C161T polymorphisms were in linkage disequilibrium (D':0.511, r2:0.099). It was determined that carrying ProPro-T161 risky PPARgamma haplotype was associated with a higher risk of BC compared to protective Ala12-CC161 haplotype (p < 0.01, OR:7.797, 95% CI:3.521-17.263). We concluded that PPARgamma Pro12Ala and C161T polymorphisms are associated with increased BC risk, and ProPro-T161 risky haplotype, which is in linkage disequilibrium, increases this effect.

[Investigation of metabolic effects of CETP gene rs289714 variation in coronary artery patients: A case-control study]. / Koroner arter hastalarinda CETP geni rs289714 varyasyonunun metabolik etkilerinin arastirilmasi: Olgu-kontrol çalismasi.

OBJECTIVE: The aim of this study was to investigate the effects of the CETP gene rs289714 polymorphism on the serum lipid profile and other metabolic parameters in Turkish patients with coronary artery disease (CAD). METHODS: The CETP rs289714 variant was examined in 104 patients with CAD and 77 controls using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The CETP rs289714 genotype and allele distribution was not statistically different between the groups (p>0.05). The body mass index (BMI) values in men with CAD were higher in patients with the G allele compared with those carrying the AA genotype (p=0.05). Logistic regression analysis showed that the G allele in male CAD patients was a risk factor for a BMI of ≥ 27 kg/m2 (odds ratio: 0.269, 95% confidence interval: 0.075­0.966; p=0.044). The G allele in female patients was associated with lower HDL-C levels than the AA genotype (p=0.049). CONCLUSION: The results suggest that the CETP rs289714 polymorphism may cause risk for the development of CAD due to its effects on high-density lipoprotein cholesterol values in female patients and BMI in male patients.

Genetic polymorphisms of the SHBG gene can be the effect on SHBG and HDL-cholesterol levels in Coronary Heart Disease: a case-control study.

Sex hormone binding globulin (SHBG) level is positively associated with the high-density lipoprotein cholesterol (HDL-C) levels. The aim of this study was to investigate the effects of the SHBG gene variations (D356N, rs1799941, and P156L) on SHBG and HDL-C levels and Coronary Heart Disease (CHD) risk. The SHBG D356 N (rs6259,G > A), P156L (rs6258,C > T), and rs1799941(G > A) polymorphisms were determined in 131 male CHD patients and 55 male controls by PCR-RFLP and real-time PCR techniques. SHGB levels were measured by Electro-chemiluminescence immunoassay (ECLIA). In the patients who had SHBG levels lower than threshold 35 nmol/l value, the risk of being HDL-C levels lower than threshold 0.90 mmol/l value was observed statistically significant (p = 0.017; OR 2.522, 95% CI 1.170-5.438). The rs1799941 GG was associated with increased CHD risk when compared with the A allele carriers (GA + AA) (p = 0.019, OR 2.222, 95% CI 1.130-4.371). In addition, the rs1799941 GG genotype and D356 N N allele were associated with lower SHBG in the CHD group (p < 0.01). The logistic regression analysis also revealed the rs1799941 GG genotype was significantly associated with low SHBG in CHD patients. It was observed that Haplotype-1(rs1799941 G allele-P156L P allele-D356 N D allele) was associated with increased CHD risk, while Haplotype-2 (rs1799941 rare A allele-P156L C allele- D356 N G allele) was correlated with the decreased CHD risk (p = 0.0167). Our findings suggest that there is a positive correlation between SHBG and HDL-C levels in CHD patients, and this association might be affected by SHBG gene variations.

BMP1 5'UTR + 104 T/C gene variation: can be a predictive marker for serum HDL and apoprotein A1 levels in male patients with coronary heart disease.

Apolipoprotein A1 (Apo A1), the major protein of HDL, is secreted as a proprotein and then is cleaved by C-terminal procollagen endoproteinase/bone morphogenetic protein-1 (BMP1). BMP1 stimulates the conversion of newly secreted proapo A1 to its phospholipid-binding form. Therefore, genetic variations of BMP1 gene may affect serum ApoA1 and HDL levels. We aimed to investigate the effects of the functional 5'UTR + 104 (T/C) variant of BMP1 on serum ApoA1 and HDL levels and risk of coronary heart disease (CHD) in this study. The BMP1 5'UTR + 104 (T/C) (rs143383) variation was determined in 131 male patients with CHD and 51 male controls by real-time polymerase chain reaction technique. ApoA1 levels were measured by immunoturbidimetry. The serum Apo-A1 levels were found higher in controls with the BMP1-CC genotype than those with the T-allele (p < 0.001). Our findings show the association of this variation with serum ApoA1 and HDL-C levels which increase in the order of CT < TT < CC in the controls. No effect was found on ApoA1 and HDL-C levels in CHD patients, as it was observed in the controls. However, the BMP1-TT genotype was associated with higher triglyceride (TG) levels as compared to C-allele (p = 0.009). These discrepancies could be due to statin therapy which has dominant effects on lowering cholesterol levels comparing to TG levels. Our results indicated that the BMP1 5'UTR + 104 (T/C) variation may affect the serum ApoA1 and lipoprotein levels depending on statin therapy so that contributes to the development of CHD.

Are IVS4 SNPs of OLR1 gene associated with coronary artery disease: Is there a linkage between IVS4 SNPs?

BACKGROUND: The OLR1 gene has been identified as a candidate gene for coronary artery disease (CAD). Six single-nucleotide polymorphisms (SNPs) of the OLR1 gene located within intron 4 (IVS4-27G>C, IVS4-73C>T, IVS4-14A>G), intron 5 (IVS5-70A>G, IVS5-27G>T) and 3'UTR (188C>T) comprise a linkage disequilibrium (LD) block, which is strongly associated with the elevated risk of CAD. OBJECTIVES: We aimed to investigate the effects of the OLR1 IVS4-14A>G and -73C>T SNPs on metabolic parameters in Turkish CAD patients, and the linkage between these 2 genetic variants. MATERIAL AND METHODS: The present study was carried out in 97 CAD patients and 78 healthy individuals. The OLR1 IVS4 genotypings were performed by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Serum high-density lipoprotein (HDL) cholesterol levels and body mass index (BMI) were higher in control subjects with IVS4-73CC genotype than in T allele carriers (CT+TT) (respectively, p = 0.002 and p = 0.024), while BMI values were lower in patients with CC genotype (p = 0.046). Patients with IVS4-14G allele (AG+GG) had a statistically higher low-density lipoprotein (LDL) cholesterol level (p = 0.027) than patients with -14AA genotype. Also the systolic blood pressure (SBP) levels were statistically higher in IVS4- 73C allele carriers (CT+CC) than in non-carriers (TT) (p = 0.045). A strong linkage between IVS4-14A>G and -73C>T SNPs of the OLR1 gene was detected in patients (D > 0.76). CONCLUSIONS: Our results indicated that the intron 4-14A>G and -73C>T SNPs of the OLR1 gene can be inherited together. The present data also suggests that the OLR1 gene may contribute to the development of hypercholesterolemia in patients with CAD.