Ozturk Ozdemir

Frequencies of micronuclei (MNi), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs) in farmers exposed to pesticides in Çanakkale, Turkey

This study aimed to determine the incidence of micronuclei (MNi), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs) in peripheral blood lymphocytes due to direct exposure to pesticides among 46 farmers in Çanakkale, Turkey. 48 non-exposed individuals living in the same socioeconomic conditions were chosen as control. In addition, a cytokinesis-block proliferation index (CBPI) was calculated. MNi and NBUDs frequencies were significantly higher among the farmers (p < 0.05). Although the NPB frequency of the farmers was higher than the controls, there was no statistical difference. Multiple linear regression analysis showed that apart from gender, no significant effects of various confounding factors were observed. Regarding CBPI, data obtained for the controls were higher than that of the farmers; however, there was no statistically significant difference.

Association between ABCB1 (MDR1) Gene 3435 C>T Polymorphism and Colchicine Unresponsiveness of FMF Patients

The multidrug resistance gene-1 (MDR1, adenosine triphosphate-binding cassette transporter: ABCB1, P-glycoprotein) encodes membrane proteins that play a crucial role in protecting cells from xenobiotics, chemicals, and drugs. The TT genotype of 3435 codon in exon 26 of MDR1 gene causes overexpression of gene activity and effluxes many chemically diverse compounds across the plasma membrane. We studied the association between C3435T polymorphisms (single nucleotide polymorphism) of MDR1 gene and colchicine-resistant familial Mediterranean fever (FMF) patients. Total genomic DNA samples from 52 FMF patients of colchicine unresponsiveness were used for FMF (MEFV) and MDR1 genes profile analyses. Target genes were genotyped by multiplex PCR-based reverse-hybridization Strip Assay method. The preliminary current results showed increased T allele frequency (0.596) in colchicine unresponsiveness of FMF patients. The distributions of the CC, CT, and TT genotypes in colchicine nonresponder FMF patients were 17%, 46%, and 37%, respectively. Our results indicate that C3435T polymorphism in exon 26 of MDR1 gene is associated with colchicine resistance in nonresponder FMF patients during the common therapy protocol.

Combined point mutations in codon 12 and 13 of KRAS oncogene in prostate carcinomas

Prostate cancer is a common malignancy that develops by structural mutation(s) and/or other genetic alterations in specific genes.The G to T transversions in codon 12 and C to T transitions in codon 13 of KRAS proto-oncogene are predominant point mutations that occur in about 20% of different cancers in human. In the current study it was aimed to investigate the prevalence and predictive significance of KRAS mutations in patients with prostate carcinomas. In a total of 30 fresh tumoural tissue specimens were investigated in patients with prostate carcinoma. All tumoural specimens were histo-pathologically diagnosed and genotyped for codon 12, 13 KRAS point mutations by reverse hybridisation and direct sequencing methods. KRAS mutations were found in 12 (40%) samples with 29 samples deriving from adenocarcinomas and 1 sample was small cell prostate carcinoma. In 1 (3.44%) sample codon 12 was found to be mutated and in 2 (6.8%) samples codon 13 and in 9 (31%) samples combined codon 12 and 13 were found to be mutated particularly in higher grade of tumoural tissues. Our study, based on representative collection of human prostate tumours, indicates that combined mutations in codons 12 and 13 KRAS are relatively infrequent and most commonly occur in prostate carcinomas.

Single-nucleotide polymorphism in Turkish patients with adolescent idiopathic scoliosis: Curve progression is not related with MATN-1, LCT C/T-13910, and VDR BsmI

The role of genetics in the etiopathogenesis of adolescent idiopathic scoliosis (AIS) is unclear. In this study, we investigated the relationship between AIS and polymorphisms in MATN‐1, LCT C/T‐13910, and VDR BsmI genes. 53 Turkish adolescents with diagnosed AIS and 54 healthy adult individuals were included in the study. MATN‐1, LCT C/T‐13910, and VDR BsmI gene mutations were analyzed with real‐time PCR. We did not detect a statistically significant difference between AIS and control groups in respect to those three different gene polymorphisms (p < 0.05). We next evaluated the associations of all three SNPs with scoliosis curve severity. There was no significant difference between curve severity and gene polymorphisms (p < 0.05). In terms of gene polymorphisms, AIS patients with a family history of AIS did not significantly differ from AIS patients who did not have history (p < 0.05). AIS might be caused by many different gene mutations, biomechanical mechanisms that have been modified by environmental factors, different biological interactions, modulation of growth, or a synergy of different factors causing abnormal control of growth. However, the existing knowledge is still not enough to explain the etiopathogenesis of AIS.

Bcıı--RFLP profiles for serum amiloid A1 and mutated MEFV gene prevalence in chronic renal failure patients requiring long-term hemodialysis.

Abstract Background and aim: There is an increased mortality risk in long-term hemodialysis patients of renal failure due to the chronic inflammation. The relationship between the chronic renal failure (CRF) and the role of familial genetic markers remains incompletely understood. In the current study, it was aimed to find out the prevalence of common MEFV gene mutations and BcII polymorphism in serum amyloid A1 (SAA1) gene in chronic renal patients (CRF) who require long-term hemodialysis. Method: Current cohort includes 242 CRF patients and 245 healthy individuals from the same population. Total genomic DNA was isolated from peripheral blood–EDTA samples and genotyping of target MEFV gene was carried out by reverse hybridization Strip Assay and real-time techniques. The SAA1 gene was genotyped by the BclI-RFLP method. Results: Increased mutated MEFV genotypes were found in current CRF patients when compared with the control group from the same ethnicity and the difference was statistically significant (Table 2) (OR: 4.9401, 95% CI: 3.0694–7.9509), p < 0.0001. The most frequent point mutations were M694V and E148Q. The mutated T allel frequency in the SAA1 gene was also different when compared with the healthy controls and the difference was found to be statistically significant (χ2: 13.18; p = 0.000). Conclusions: The current results indicate the germ-line mutations in both genetic biomarkers (MEFV and SAA1 genes) that are related to inflammation and amyloidosis processes may play a crucial role in CRF pathogenesis due to the long-term chronic inflammation.

Endothelial function and germ-line ACE i/d, eNOS and PAI-1 gene profiles in patients with coronary slow flow in the Canakkale population: multiple thrombophilic gene profiles in coronary slow flow

Summary Background We examined the effects of ACE, PAI-1 and eNOS gene polymorphisms on endothelial function. The genes are related to atherosclerosis and endothelial dysfunction in coronary slow flow (CSF). Methods Thirty-three patients with angiographically proven CSF and 48 subjects with normal coronary flow were enrolled in this study. Coronary flow patterns were determined by the thrombolysis in myocardial infarction (TIMI) frame count method. Endothelial function was assessed in the brachial artery by endothelium-dependent flow-mediated dilatation (FMD). PAI-1 4G/5G, eNOS T-786C and ACE I/D polymorphisms were determined by polymerase chain reaction (PCR) amplification. Results No difference was found between the groups regarding age, heart rate and blood pressure. Males were more prevalent among patients with CSF than control subjects (58.8 vs 29.8%, p = 0.009). Mean TIMI frame counts were significantly higher in CSF patients (24.2 ± 4.0 vs 13.1 ± 2.5 fpm, p = 0.001). FMD was significantly lower in CSF patients than in the controls (4.9 ± 6.6 vs 7.9 ± 5.6%, p = 0.029). TIMI frame count and FMD were found to be negatively correlated in a correlation analysis (r = –0.269, p = 0.015). PAI-1 4G/5G, eNOS T-786C and ACE I/D polymorphisms were similar in the two groups. Conclusions This study showed that endothelial function was impaired in patients with CSF. PAI-1, ACE and eNOS polymorphisms were not related to CSF in our study population.

In Vivo Evaluation of the Genotoxic Effects of Gonadotropins on Rat Reticulocytes

BACKGROUND Gonadotropins, as ovulation-inducing drugs, have been used widely to treat infertility. An epidemiologic correlation between infertility therapy and ovarian cancer development has been reported. However, the effect of gonadotropins in the formation of reproductive tract cancers is controversial. OBJECTIVE The aim of the study was to determine the in vivo genotoxic effects of gonadotropins on rat reticulocytes. METHODS In this prospective, randomized, controlled study, rats were randomly assigned to 1 of 5 groups. The calculated rat doses of 0.65 human menopausal gonadotropin (hMG), 0.95 hMG, 0.65 follitropin beta (FB), 0.95 FB, or normal saline (control group) were injected, respectively. These calculated rat doses (U/g) are based on average human gonadotropin doses of 150 and 225 IU/d for a 70-kg woman given in 2-mL saline (the control group received 2 mL of saline). Injections were administered once per day for 5 days, followed by 5 days of rest. Each treatment was repeated for 6 estrus cycles in the rats for a total of 12 estrus cycles. Six months after the last day of the 12(th) cycle, the rats were euthanized. Bone marrow tissues were removed, and pluripotent reticulocyte cells with micronuclei, nuclear buds, and binuclear abnormalities were analyzed using an in situ micronuclei assay under light microscopy. The proportion of micronucleated cells, cells with anaphase bridge, nuclear buds, and other nuclear abnormalities were measured. RESULTS The number of cells with nuclear buds and binuclear abnormalities in the hMG 225 and FB 225 groups was significantly higher (P < 0.05) than that from the hMG 150, FB 150, and control groups in the cytogenetic analysis of bone marrow stem cells. An increased rate of genotoxicity in all gonadotropin groups versus that of placebo was found. CONCLUSION In rats, the micronucleus genotoxicity assay suggests a dose-dependent gonadotropin effect on genomic instability in bone marrow stem cells in vivo.

Possible association between germline methylenetetrahydrofolate reductase gene polymorphisms and psoriasis risk in a Turkish population

Psoriasis is a common chronic inflammatory skin disease caused by genetic and epigenetic factors. There are conflicting results in the literature about the association between psoriasis and the methylenetetrahydrofolate reductase gene (MTHFR), ranging from strong linkage to no association.

The relationship between C-reactive protein rs3091244 polymorphism and ankylosing spondylitis.

Previous studies have shown that C‐reactive protein (CRP) gene polymorphism can be related to inflammatory changes. The present study aimed to examine the association between CRP gene polymorphism and clinical and laboratory findings in ankylosing spondylitis (AS) patients.

Association Between Inherited Thrombophilia and Impaired Right Ventricular Function in Deep Vein Thrombosis Without Symptomatic Pulmonary Embolism

The aim was to evaluate the right ventricular function in patients with inherited thrombophilia and deep vein thrombosis (DVT) without pulmonary embolism. A total of 38 patients with DVT without symptomatic pulmonary embolism and 30 patients with varicose veins were enrolled. Clinical data, echocardiography, and 2 thrombophilic mutations were analyzed. Factor V Leiden (FVL) polymorphism was significantly frequent in the study group (P = .007). The difference in prothrombin G20210A polymorphism between the study and control groups was at a near-significant level (P = .058). There was statistically significant decrease in tricuspid annular plane systolic excursion values in patients with FVL and prothrombin G20210A polymorphism. Combined FVL and prothrombin G20210A polymorphisms were more closely related to the decrease in this value (P = .006). Deep vein thrombosis had no additional adverse effects on right ventricle. Impaired right ventricular systolic function occurs in FVL and prothrombin G20210A polymorphisms.