The role of single nucleotide polymorphisms of miRNAs 100 and 146a as prognostic factors for prostate cancer

Introduction: Prostate cancer has a high incidence in men and is the second cause of cancer death among americans male. microRNA (miR) is becoming a potential new prognostic factor for prostate cancer. Single nucleotide polymorphisms (SNPs) are common polymorphisms, characterized by a single exchange of nitrogen based in the DNA. This polymorphism is present in the miRs, altering their function. Objective: To evaluate the role of SNP rs1834306 of miR100 and rs2910164 of miR146a in the development and prognosis of prostate cancer. Methods: One hundred patients diagnosed with prostate cancer and 68 controls were selected. The identification of SNP was rated by quantitative polymerase chain reaction from blood samples, and the analysis was performed within the presence of SNP and the prognostic variables. Results: In the SNP rs1834306 (miR100), a smaller presence of the polymorphic homozygous genotype was identified in patients with PSA >10 ng/mL, ( P=0.03); when evaluating only the presence of the polymorphic allele G ( P=0.09) it was compared to the presence of the wild type allele A. Among the patients with prostate cancer, SNP rs2910164 (miR146A), the polymorphic allele was more frequent in patients with a Gleason score ⩾7 than in patients with a Gleason score <7, ( P=0.043). In patients with prostate cancer, miR100 was overexpressed in those with pT3 staging compared to pT2 and among those who had biochemical recurrence ( P = 0.004 and P = 0.011, respectively). Conclusions: SNP of miR146a acts as a poor prognostic factor (Gleason ⩾7), and the SNP of miR100 is linked to better prognostic data (PSA <10). MiR100 was overexpressed in prostate cancer with worse prognostic factors.

COMPARATIVE CHARACTERISTICS OF POLYMORPHIC ALLELES PROPAGATION IN THE GENES SYSTEM HEMOSTASIS (PAI-1 (- 675 5G / 4G) AND THE FGB (- 455 G / A)) IN SUDDEN CARDIAC DEATH AND ACUTE CORONARY SYNDROME IN PATIENTS UNDERGOING CORONARY ARTERY STENTING

The purpose of this study was to give a comparative characteristics of the prevalence of polymorphic alleles in the genes of the hemostatic system (PAI-1 (- 675 5G / 4G) and FGB (- 455 G / A)) in patients with sudden cardiac death and acute coronary syndrome in patients undergoing coronary artery stenting. Material and methods. Genetic typing of biological material (BM) was performed for the prevalence of polymorphic alleles in two genes of the hemostasis system. BM was selected from people with a diagnosis of coronary artery disease, divided into three comparison groups: I - suddenly deceased citizens with a diagnosis of coronary artery disease, II - patients with ACS who underwent urgent coronary artery stenting, III - patients with a chronic form of coronary artery disease endovascular surgery was performed as planned. Results and discussion. The calculated criterion 2 of the prevalence of polymorphisms in the FGB (- 455 G / A) and PAI-1 (- 675 5G / 4G) genes turned out to be more than the critical (tabular) value, which indicates the existing relationship between the presence of IHD and the carriage of one of polymorphic alleles. Based on the same data, the 2 criterion was calculated without taking into account data for a group of healthy citizens. For carriers of the polymorphic allele of the FGB gene (- 455 G / A), no statistically significant differences were found. For carriers of the PAI-1 gene polymorphic allele (- 675 5G / 4G), statistically significant differences were found. Conclusions. ACS with a favorable outcome (subject to emergency surgical intervention) occurs at an earlier age compared to suddenly dead citizens diagnosed with coronary artery disease. The presence of a mutant allele in the PAI-1 gene (- 675 5G / 4G) requires further studies in order to expertly assess the death rate in patients after surgery with coronary stenting.

Effect of thiazolidinediones on dislipidemia in patients with metabolic syndrome depending on the gene PPAR-gamma rs1801282 polymorphism

Background. To evaluate the effect of thiazolidinediones on lipid spectrum of blood in patients with metabolic syndrome depending on gene polymorphism rs1801282. Materials and methods. The study included 109 patients with newly diagnosed metabolic syndrome. All subjects in the study underwent general clinical, laboratory methods, presence of polymorphism rs1801282 of the PPAR-gamma gene was also determined. All patients were recommended to keep a diet, increase physical activity and receiving pioglitazone 30 mg per day for the period of 3 months. Results.During therapy with pioglitazone it was noted that the degree of reduction of triglycerides was more pronounced in patients with IGT carrying rs1801282 -1.2 (-1.7; -1.1) versus -0.2 (-0.4; 0.0) in patients with wild genotype (p < 0.001) as well as in patients with type 2 diabetes, carries of polymorphic allele -1.3 (-1.6; -1.2) versus -0.2 (-0.3; 0.0) in patients with wild genotype (p < 0.001). Conclusion. As a result of administering pioglitazone, an improvement in the lipid spectrum of the examined patients was noted. The maximum degree of reduction of triglycerides was observed in patients carrying rs1801282 polymorphic allele compared with the wild genotype.

EFFECT OF CYTOCHROME P450 2C9 GENE POLYMORPHISMS ON INDIVIDUAL SENSITIVITY TO GLICLAZIDE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Cytochrome P450 2C9, encoded by the gene CYP2C9 , is a key enzyme for the metabolism of most sulfonylurea (SU). It is known that the polymorphisms CYP2C9*2 and CYP2C9*3 are associated with decreased activity of cytochrome, which leads to an increase in plasma concentrations of SU and reduction in its clearance. The aim of the study was to assess the impact CYP2C9 polymorphisms on individual sensitivity to gliclazide in patients with type 2 diabetes. The study included 74 patients with newly diagnosed diabetes. For all patients gliclazide in a dose of 30 or 60 mg/day was prescribed. Dose titration was carried out for 6 months of observation. If necessary other glucose-lowering therapy (a combination of drugs or insulin) were prescribed. Following the results of study, all patients had achieved the target values of Hb A1c. In comparison with patients who had a polymorphic allele in the gene, patients with wild-type CYP2C9 had lower effective dose of gliclazide, more often required prescription of large (90-120 mg) doses of drug or other antihyperglycemic therapy. Conclusion: The presence of a polymorphic allele in the gene CYP2C9 in homo- or heterozygous state is associated with a decrease in the effective dose of gliclazide, used as monotherapy in patients with type 2 diabetes.

C950T and C1181G Osteoprotegerin Gene Polymorphisms In Myeloma Bone Disease

Bone disease is one of the hallmarks of multiple myeloma (MM). The role of osteoprotegerin (OPG) in the RANK/RANKL/OPG signaling system is well defined in the myeloma bone disease. Polymorphisms of the TNFRSF11B gene encoding OPG have been studied in various bone diseases. However, relationship between the levels of OPG and development of bone lesions regardless of RANKL is yet unknown. In this study, the effects of OPG gene polymorphism on the development of bone lesions in MM were investigated. 52 MM patients, admitted to Karadeniz Technical University, Medical Faculty, Department of Internal Medicine, Division of Hematology between March 2011 and March 2012, were included into the study. Pathologic fracture and/or destructive bone lesions were confirmed in 36 MM patients using X-ray, computed tomography (CT), or magnetic resonance imaging (MRI). No bone lesions were noted in 16 patients. The control group consisted of 20 age and gender matched volunteers. Exon 1 of OPG gene was sequenced using DNA samples obtained from peripheral blood samples of 52 MM patients and 20 healthy control subjects. OPG gene C950T and C1181G polymorphisms were identified in 45 (33 with bone lesions) MM patients and in 16 control subjects. Polymorphic allele 1181G was higher in MM patients with bone lesions compared to MM patients without bone lesions and control group (χ2=8.629, p=0.013). Other polymorphic allele 950T was also overrepresented (73%; p=0.042) in MM patients with bone lesions compared to MM patients without bone lesions and the control group. The most frequent genotype observed in patients with myeloma bone lesions was 950 TT homozygous variant (56%, p=0.08) followed by 1181 CC homozygous wild type with 50% frequency (p=0.09). The frequency of 950 CT heterozygous genotype was higher in MM patients without bone lesions (50%, p=0.604). 1181 GG genotype showed higher frequency in MM patients with bone lesions compared to patients without bone lesions and control group (χ2=3.853, p=0.145). Of the combined haplotypes, 950 TT/1181 GG haplotype frequency is higher in patients with myeloma bone lesions (36%) compared to MM patients without bone lesions (13%) and controls (15%) (χ2=4.77, p=0.09). The frequency of TT/GG combined haplotype carriers in bone disease patients is higher than of those who do not have either polymorphic homozygous alleles (CT/CC and CC/CC haplotypes) (χ2=6.057, p=0.048). Additionally, 950 CC/1181CC wild type haplotype frequency was reasonably low in patients with myeloma bone lesions (8.3%, p=0.240). This is the first study searching for the relationship between OPG gene variants C950T (promoter), C1181G (exon 1) and myeloma bone disease. It was concluded that the presence of polymorphic 1181 G/950 T alleles and 950 TT/1181 GG genotypes may play a role in the development of bone disease. Disclosures: No relevant conflicts of interest to declare.