İsmail Benli

Cardiotrophin-1 plasma levels are increased in patients with diastolic heart failure

Summary Background Cardiotrophin-1 (CT-1) is a member of the interleukin (IL-6) family of cytokines and is increased in various cardiovascular diseases, including chronic heart failure. The aim of the study was to determine if plasma CT-1 is associated with diastolic heart failure (DHF) and to investigate the relationship between CT-1 and echocardiographic parameters. Material/Methods Fifty-seven consecutive patients (mean age 57±8 years, 24 males) diagnosed with DHF in our clinic and 33 controls (mean age 55±7 years, 12 males) were included in the study. All study participants underwent echocardiographic evaluation and blood samples were obtained. Results CT-1 and NT-proBNP values were significantly higher in DHF subjects than in controls (11.30 [8.09–16.51] vs. 17.5 [8.95–28.74] fmol/mL, P=0.017 and 64 [27.5–95] vs. 82 [55.5–241] pg/mL, P=0.009, respectively). The mitral peak velocity of early diastolic filling (E), mean ratio of E to early diastolic mitral annular velocity (E/Em), and the pulmonary capillary wedge pressure (PCWP) estimated from E/Em measurements were all significantly higher in the patient group (62.27±14.69 vs. 75.67±18.85 cm/sec, 6.40±1.48 vs. 10.30±3.48, and 10 [9–11]vs. 14[12–16] mmHg, P≤0.001 for all). Lateral and septal Em were significantly lower in the patient group (10.69±1.87 vs. 8.69±2.00 cm/sec and 8.91±1.22 vs. 6.65±1.58 cm/sec, P<0.001 for both). CT-1 positively correlated with NT-proBNP (P=0.001, r=0.349), mean E/Em (P=0.003, r=0.307), and estimated mean PCWP (P=0.001, r=0.308). Conclusions CT-1 is elevated in patients with DHF and is associated with NT-proBNP and estimated left ventricular filling pressures.

Association of MMP2-1306C/T and TIMP2G-418C polymorphisms in retinal vein occlusion.

Matrix metalloproteinases (MMPs) are large groups of zinc-dependent proteases that play an important role in many diseases and pathological processes such as cancer, angiogenesis, atherosclerosis, and vascular disease. Also, it was found that the expression of MMPs was high during the initial period of thrombosis in a rat model of traumatic deep vein thrombosis. Moreover, the presence of metalloproteinase activity and endogenous inhibitor activity in vitrectomy samples are associated with neovascularization of several retinal diseases such as exudative age related maculopathy, proliferative diabetic retinopathy, and central retinal vein occlusion. In this study, we aimed to investigate the possible association of the matrix metalloproteinase 2-1306C/T (rs 243865) and tissue inhibitors of matrix metalloproteinase 2 G-418C (rs 8179090) polymorphisms with the risk of retinal vein occlusion (RVO). Genomic DNA was extracted from peripheral leukocytes from ethylenediaminetetraacetic acid anticoagulated blood. Genotyping of the MMP2-1306C/T and TIMP2G-418C polymorphisms were performed using real-time polymerase chain reaction. The MMP2-1306 T allele carriers (CT + TT) had a significantly increased risk of RVO compared with the CC homozygotes (p < 0.001, odds ratio = 4.78; 95% CI = 2.85-8.09). After adjusting for hypertension, diabetes, hypertriglyceridemia, and hypercholesterolemia, MMP2-1306 T allele carriers (CT + TT) also had a significantly increased risk of RVO (B = 1.453; p < 0.001; odds ratio = 4.275; 95% CI:2.529-7.224). MMP2-1306C/T, but not TIMP2G-418C, gene variants are a risk factor for the development of retinal vein occlusion.

The Role of MMP2 (-1306C>T) and TIMP2 (-418 G>C) Promoter Variants in Age-related Macular Degeneration

Abstract Purpose: To investigate the possible association between the matrix metalloproteinase 2 (-1306C>T) (rs 243865) and tissue inhibitors of matrix metalloproteinase 2 (-418 G>C) (rs 8179090) polymorphisms and the risk of age-related macular degeneration. Methods: This case-controlled prospective study included 144 age-related macular degeneration patients and 172 control subjects. All subjects were screened for age, gender, hypertension (HT), diabetes (DM), and body mass index (BMI). Serum levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), total cholesterol (TC), and smoking were also determined. Genomic DNA was extracted from peripheral leukocytes from ethylenediaminetetraacetic acid anticoagulated blood. Genotyping of the MMP2 (-1306C>T) and TIMP2 (-418 G>C) polymorphisms was performed using real-time polymerase chain reaction. Results: Genotype distributions or allelic frequencies of MMP2 (-1306C>T) and TIMP2 (-418 G>C) did not significantly differ between patients with AMD and control subjects. Similarly, no significant differences in either genotype distributions or allelic frequencies of MMP2 (-1306C>T) and TIMP2 (-418 G>C) were found between dry and wet AMD. Conclusion: MMP2 (-1306C>T) and TIMP2 (-418 G>C) promoter variants are unlikely to have a major role in age-related macular degeneration risk susceptibility.

Predictive value of the vitamin K epoxide reductase complex subunit 1 G-1639A and C1173T single nucleotide polymorphisms in retinal vein occlusion

Background:  To determine if vitamin K epoxide reductase complex subunit 1 gene polymorphisms have an effect on the risk of having a retinal vein occlusion.

A pilot study of the association of manganese superoxide dismutase and glutathione peroxidase 1 single gene polymorphisms with prostate cancer and serum prostate specific antigen levels.

Introduction The aim of the study was to evaluate the potential association of single gene polymorphisms of the antioxidant enzymes manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPX1) with prostate cancer (PCa). Material and methods Manganese superoxide dismutase and glutathione peroxidase 1 genotypes and allele frequencies in 49 prostate cancer cases (PCa group) and 98 control subjects were determined. Analysis of genotypes in control group individuals were performed in two subgroups according to serum prostate-specific antigen levels: the control group (n = 49), with prostate specific antigen (PSA) level < 4 ng/ml; and the nonPCa-high PSA control group (n = 49), with serum PSA > 4 ng/ml. Determination of MnSOD Ala-9Val and GPX1 Pro198Leu polymorphisms was performed using real-time polymerase chain reaction amplification. Results No association was found between GPX1 polymorphisms and PCa in all groups (p > 0.05). In the PCa group, the frequency of homozygote Val allele carriers was significantly higher in comparison to nonPCa-high PSA control cases. Therefore, Val/Val genotype was found significantly suspicious for PCa risk (OR = 2.48; 95% CI: 1.37–4.48; p = 0.002). Furthermore, an overall protective effect of the Ala allele of the MnSOD polymorphism on PCa risk was detected. These findings in this small Turkish population suggested that individual risk of PCa may be modulated by MnSOD polymorphism especially in patients with high PSA, but GPX1 polymorphism seemed to have no effect on PCa risk. Conclusions The presence of genetic variants of antioxidant enzymes could have a potential influence on genesis of prostatic malignancy.

GENETIC ASSOCIATION BETWEEN ARTERIAL STIFFNESS-RELATED GENE POLYMORPHISMS IN BRVO AND CRVO PATIENTS IN A TURKISH POPULATION.

Purpose: To investigate possible associations between five different single-nucleotide polymorphisms, from genes associated with arterial stiffness and branch retinal vein occlusion (BRVO), or central retinal vein occlusion. Methods: A total of 187 patients with retinal vein occlusion (133 with BRVO and 54 with central retinal vein occlusion), and 167 controls, were enrolled in this study. All subjects were screened for hypertension, diabetes, smoking status, body mass index, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, total cholesterol, and very low-density lipoprotein. The genotyping of adiponectin +276 G/T, ACE I/D, AGTR1 A1166C, eNOS E298D, and p22phox −242 C/T polymorphisms was performed using real-time polymerase chain reaction. Results: The percentage of the adiponectin +275 T allele carriers was significantly higher in the BRVO patients (37%) than in the controls (23%, P < 0.001). Similarly, the percentage of AGTR1 1166 C allele carriers was significantly higher in the BRVO patients (38%) than in the controls (24%, P < 0.001). At the multiple logistic regression analysis, the adiponectin +275 T allele carrier and AGTR1 1166 C allele carrier status were found to be associated with an increased risk of BRVO (TT vs. GG and TG: odds ratio = 2.278, P = 0.002, 95% confidence interval: 1.370–3.789; CC vs. AA and AC: odds ratio = 1.804, P = 0.025, 95% confidence interval: 1.079–3.017). The genotype distributions or allelic frequencies of ACE I/D, eNOS E298D, and p22phox −242 C/T did not significantly differ between the patients with BRVO and the control subjects. There was no significant difference between the central retinal vein occlusion patients and controls for the genotype or the allele frequency distributions of all evaluated single-nucleotide polymorphisms. Conclusion: Adiponectin +276 G/T and AGTR1 A1166C single-nucleotide polymorphism are likely to be risk factors for BRVO.

Association of paraoxonase 1 L55M and Q192R single-nucleotide polymorphisms with age-related macular degeneration.

Purpose: To determine if paraoxonase 1 (PON1) gene polymorphisms have an effect on the risk of having age-related macular degeneration (AMD). Methods: The study population consisted of 142 patients who were diagnosed with either exudative or atrophic AMD and 138 sex- and age-matched controls without AMD. Genotyping of the PON1 L55M and Q192R single-nucleotide polymorphisms was performed using real-time polymerase chain reaction and commercially produced kits. A full ophthalmic evaluation was performed in each subject, and all subjects were screened for hypertension, diabetes, hypercholesterolemia, and smoking history. Results: The PON1 MM and QQ genotypes were less frequent in patients with AMD than in control subjects (MM: 4 vs. 13%, P = 0.015; QQ: 15 vs. 27%, P = 0.020). A multivariate logistic regression analysis was also conducted. After adjusting for age, gender, and the prevalence of smoking, hypertension, diabetes, and hypercholesterolemia, the MM and QQ genotypes (MM/QQ vs. LL + LM/QR + RR) were found to be associated with a decreased risk of AMD (MM: odds ratio = 0.24, P = 0.007, 95% confidence interval: 0.09–0.68; QQ: odds ratio = 0.46, P = 0.013, 95% confidence interval: 0.25–0.85). Conclusion: The authors found that subjects with the PON1 MM and QQ genotypes had a lower risk of AMD.

Serum levels of gamma-glutamyl transferase are associated with cardiovascular disease in obstructive sleep apnea syndrome.

BACKGROUND AND OBJECTIVES Obstructive sleep apnea syndrome (OSAS) significantly increases the risk of cardiovascular disease (CVD). γ-glutamyl transferase (GGT) is a new marker for predicting CVD. The aim of this study was to evaluate the relationship of serum GGT levels with cardiovascular event, severity of OSAS, and polysomnographic parameters in patients with OSAS. DESIGN AND SETTINGS This was a retrospective, cross-sectional study conducted between January 2011 and March 2013 (Gaziosmanpasa University, Faculty of Medicine, Tokat, Turkey). METHODS We performed a retrospective study. Patients were divided according to their apnea-hypopnea index (AHI) scores into OSAS negative (AHI< 5, Group 1), mild OSAS (AHI: 5–15, Group 2), moderate OSAS (AHI=15–30, Group 3), and severe OSAS (AHI > 30, Group 4) groups. The presence of heart failure, coronary artery disease, or arrhythmia was defined as CVD. RESULTS A total of 320 patients, with a mean age of 50.2 (10.8) years, were included in this study. There were 47, 68, 58, and 147 patients in Groups 1, 2, 3, and 4, respectively. Serum GGT levels were significantly different between groups (Group 1: 25.24 [14.95]; Group 2: 28.03 [11.92]; Group 3: 32.82 [18.18], and Group 4: 40.41 [31.90] mg/dL, P<.001). Besides, serum GGT levels were significantly correlated with AHI, oxygen desaturation index, and average and minimum O2 saturation values (P<.05). Serum GGT levels were significantly higher in patients with CVD compared with those without (P<.05). Multiple regression analysis demonstrated that independent predictors of CVD were serum GGT and low-density lipoprotein-cholesterol levels, age, and body mass index in patients with OSAS. CONCLUSION GGT level is an important predictor for CVD in patients with OSAS. The effectiveness of continuous positive airway pressure therapy on CVD and GGT levels should be investigated.

Oxidative Stress And Prolidase Enzyme Activity In The Pathogenesis Of Primary Varicose Veins

Objectives Vascular endothelial dysfunction leads to the emerging of free oxygen radicals, deficiency of antioxidant system, forming of oxidative stress, inflammatory processes and release of proinflammatory cytokines. These things play big role in the development of primary varicose veins. Prolidase has been reported as an indicator of oxidative stress in diabetes, diabetic neuropathy, non-ulcerous dyspepsia, osteoporosis, polycystic over syndrome and many other diseases. The aim of this study is to evaluate the oxidative stress at venous insufficiency and to provide preliminary knowledge about the role of prolidase enzyme in varicose vein formation. Methods Ninety patients aged between 22 and 80 (47.35 ± 17.69) were included in the study and divided into 3 groups. Group1(n:30)(Serum control group): Patients without venous insufficiency. Group 2(n:30)(Tissue control group(healthy vein group): Patients underwent coronary artery bypass surgery (the remaining portion of great saphenous vein used as coronary artery bypass graft used as normal tissue) . Group 3(n:30)(Varicose vein group): Patients underwent varicose vein surgery (varicose vein and serum of these patients were used for study). Total Oxidant Status (TOS), Total Antioxidant Status (TAS), Oxidative Stress Index (OSI) and Prolidase enzyme levels were detected in tissue and serum samples. Results No significant changes were detected between three groups’ serum samples in oxidative stress parameters and in the prolidase enzyme activity. The tissue TOS and OSI were higher in varicose vein group according to normal vein group and this was found statistically significant. And TAC levels in varicose vein group were significantly lower than normal vein group. Prolidase enzyme activity in varicose vein group was found higher according to normal vein group. Conclusion Oxidative stress plays a role at the development of primary varicose veins at biochemical level. Prolidase enzyme related with oxidative stress may play an important role in the pathogenesis of primary varicose veins.

Assessment of local and systemic 25-hydroxy-vitamin D, RANKL, OPG, and TNF levels in patients with rheumatoid arthritis and periodontitis

The present study aimed to evaluate proinflammatory cytokine and vitamin D levels in rheumatoid arthritis (RA) and chronic periodontitis (CP) patients and healthy individuals before and after initial periodontal treatment. Overall, 17 CP patients with RA (RA + CP), 18 systemically healthy CP patients (CP), and 18 healthy controls (C) were included. Clinical periodontal measurements were recorded and gingival crevicular fluid (GCF) and blood samples were recorded. RA + CP and CP patients received nonsurgical periodontal treatment. Vitamin D, tumor necrosis factor (TNF)-α, receptor activator of nuclear factor-KB ligand (RANKL), and OPG levels were determined in GCF and serum. Baseline clinical parameters were similar in all periodontitis groups (P > 0.05) but were higher than that in controls (P < 0.05). Periodontal treatment improved clinical parameters in all periodontitis groups (P < 0.05). GCF vitamin D levels were higher in RA + CP and CP groups than in healthy controls, but these levels decreased in the RA + CP group after periodontal treatment (P < 0.05). Serum RANKL and GCF TNF-α levels in RA patients decreased after periodontal treatment (P < 0.05). Within the limitations of this study, the results suggested that GCF vitamin D levels are increased in RA patients and decrease after periodontal treatment; therefore, local vitamin D levels might be an important indicator of periodontal bone loss.