The role of caveolin-1 and endothelial nitric oxide synthase polymorphisms in susceptibility to prostate cancer.

Caveolin-1(cav-1) is overexpressed in prostate cancer (PC) and is associated with progression of the disease. We investigated the effects of CAV1-T29107A and endothelial nitric oxide synthase (eNOS) G894T polymorphisms on the serum levels of testosterone, NO and prostate-specific antigen (PSA) in patients with PC. We genotyped cav-1 and eNOS genes in 112 PC patients and 150 healthy controls by PCR-RFLP. Serum levels of NO2- and NO3- were measured using spectrophotometry, and serum levels of testosterone and PSA were measured by ELISA. The frequencies of CAV1 genotypes A/T vs. A/A according to the dominant model AT + TT vs. AA genotype and T allele were significantly higher in PC patients in comparison with the control group and considerably increased the risk of disease by 2.19-, 1.44- and 1.6-fold, respectively. AT + TT genotypes were associated significantly with the increased risk of PC in those with smoking or diabetes by 3.08-fold (P = .004). Individuals carrying concurrently the T allele of CAV1 A29107T and the T allele of eNOS G894T genes had a significantly increased risk of PC by 2.52-fold (P = .009). We did not find any significant relationship between eNOS G894T genotypes and alleles with susceptibility to PC. Our results highlighted the significance of CAV1-T29107A SNP but not (eNOS) G894T in the susceptibility to PC in our the population that we have studied.

Activities and polymorphisms of MMP-2 and MMP-9, smoking, diabetes and risk of prostate cancer.

Matrix metalloproteinases (MMPs) are a group of zinc dependent enzymes that are involved in tumor cell invasion and metastasis. The role of MMP-2 and -9 genetic polymorphism in different malignancies has been the subject of numerous studies. The present research has attempted to discover any positive correlation between MMP-2 and MMP-9 SNPs and prostate cancer (PCa) in patients with a history of either diabetes or smoking habits. 112 PCa-patients and 150 unrelated healthy-controls that matched for age and sex were selected for present case-control study. MMP-2 -1575G/A and MMP-9 -1562 C/T polymorphisms detected by PCR-RFLP, serum tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), testosterone, prostate-specific antigen (PSA), free-prostate-specific-antigen (fPSA), and fPSA/PSA levels were detected by ELISA and enzyme assay, respectively. MMP-2 and MMP-9 activities were measured by gelatin-zymography. Covariates were considered as age, status of cigarette smoking, and a possible history of diabetes mellitus (DM). The frequency of -1575 MMP-2 A/A + A/G and -1562 MMP-9 C/T + T/T genotypes were higher in PCa-patients with DM (74.3%,p = 0.003) and with smoking habits (72.5%,p = 0.005). These genotypes were associated with the increased risk of prostate cancer in smokers (3.52-folds) and in individuals with history of DM (4.34-folds). A significant positive association was found between level of TIMPs (TIMP -1 and TIMP-2) and BMI in PCa-patients and also between testosterone levels and MMP-9 activity in healthy control subjects. For the first time, this study demonstrated that activities of MMP-2 -1575G/A and MMP-9 -1562C/T variants in association with smoking and diabetes are considered significant risk factors for PCa.

Vitamin D-binding protein and vitamin D receptor genotypes and 25-hydroxyvitamin D levels are associated with development of aortic and mitral valve calcification and coronary artery diseases.

To assess the association between vitamin D-Binding Protein (VDBP rs7041T>G) and vitamin D receptor (VDR rs1544410G>A) gene polymorphisms with susceptibility to cardiovascular diseases in population from west of Iran. Two hundred forty-nine individuals with cardiovascular disease (92 with aortic and Mitral Valves Calcification (AMVC) and 157 with Coronary Artery Diseases (CAD) that their diseases were confirmed by echocardiography and angiography and unrelated 182 healthy controls (gender and age-matched) were selected for this case-control study. The VDR 1544410G>A, and VDBP 7041T>G genotyping were detected by PCR-RFLP, serum vitamin D and lipid concentrations were measured by ELISA and enzyme assay, respectively. The VDR rs1544410G>A gene is a strong risk factor for CAD (OR = 1.28, p = 0.002) and the dominant genotype (T/G+G/G) of VDBP 7041 T>G SNP plays a protective role (OR = 0.67, p = 0.003) in AMVC development in studied population. In addition, lower level of vitamin D strongly increased the risk of CAD (15 ± 11.02 vs. 21.3 ± 18 µg/L, p = 0.043) and AMVC (12.1 ± 13.1 vs.21.3 ± 18 µg/L, p = 0.014) development in individuals carrying T/T genotype of VDBP 7041 T>G gene polymorphism. There was a strong interaction between A allele VDR rs1544410 and G allele of VDBP rs7041 genes in a protective role (OR = 0.74, p = 0.044) in AMVC patients). CAD and AMVC patients were deficient in vitamin D, i.e. their level of vitamin D was strongly lower than that in the control group. Our findings for the first time indicated that there is a strong association between vitamin D deficiency, lipid profile and the VDR rs1544410G>A and rs7T41>G VDBP genes polymorphisms. These interactions may be one of the important factors for CAD and AMVC incidence.