Polymorphisms of eNOS, catalase, and myeloperoxidase genes in prostate cancer in Turkish men: preliminary results.

Prostate cancer (PCa) is the most common type of neoplasm in European males. Genetic and epigenetic factors contribute to PCa development and progression. In this study, we aimed to assess the relationship between PCa and polymorphisms in the genes encoding endothelial nitric oxide synthase (eNOS), catalase (CAT), and myeloperoxidase (MPO). In total, 193 patients were included in the study. Patients were divided into three groups: PCa (78), benign prostate hyperplasia (40), and control males (75). The parameters assessed included body mass index (BMI), smoking habits, presence of prostatism, prostate-specific antigen (PSA) levels, Gleason scores of prostate specimens, as well as polymorphisms in eNOS-G894T, CAT- 262T, and MPO G-463T genes. BMI and smoking status of controls and patient groups showed no significant difference. CAT-262T gene polymorphism was found to be homozygous in 35.4% of PCa patients, which was 4.02-fold that in the controls (P = 0.006). There was no statistically significant difference in eNOS-G894T and MPO G-463T gene polymorphisms between any of the groups. In conclusion, we found catalase levels to be associated with PCa diagnosis and PSA value. We did not find any significant differences between groups for other polymorphisms, but we believe that further studies with a large sample size may be needed before drawing definite conclusions.

The efficacy of tissue factor -603A/G and +5466A>G polimorphisms at the development of venous thromboembolism in cancer patients.

UNLABELLED: Venous thromboembolism (VTE) is one of the most common complications in cancer patients. Although factor V Leiden (FVL) is the most common genetic defect causing thrombosis, the impact of gene abnormalities on thrombotic tendency in cancer patients remains poorly explored. Tissue factor (TF) is a major physiologic initiator of blood coagulation. This is the first study regarding the association of TF gene -603A/G and +5466A>G polymorphisms with VTE in malignancy. Materials and Me-thods: The study consists of two groups: cancer patients with VTE were included as Group 1 (n = 46); Group 2 comprises 196 cancer patients without VTE. Restriction fragment length polymorphism method was used for the detection of polymorphisms of TF -603A/G in the 5՛upstream region and TF 5466A/G in intron 2. FVL, PT G20210A and MTHFR C677T polymorphisms were determined by using commercially available Light Cycler kits. The genotype and allele frequencies between the groups were compared using χ2 or Fisher exact test, if appropriate. RESULTS: No differences were observed in the distribution of TF gene -603A/G genotype frequencies between the groups. Although a slightly increased incidence of +5466GA genotype was in Group 1 (17.4% vs 11.2%), it did not achieve statistical significance. The prevalence of FVL was significantly greater in Group 1 compared with Group 2 (41.3% vs 4.1%, p < 0.05). Difference in frequency of 677TT+CT (MTHFR) + 5466GG (TF) genotypes combination was found in women of two investigated Groups (p < 0.05). No differences were also in genotypes and allele frequencies of MTHFR C677T and PT G20210A between two Groups (p > 0.05). CONCLUSIONS: The present study did not show significant association of TF gene -603A/G and +5466A>G polymorphisms with VTE in malignancy, however, further larger studies including different ethnic population are needed to confirm our findings.

The effect of Glutathione-S-transferases in the susceptibility to bladder cancer.

BACKGROUND: Urinary bladder cancer is a quite common cancer type in men and women all over the world. Genetic polymorphisms of xenobiotic-metabolizing enzymes could increase individual susceptibility to various cancer types. AIMS: The aim of our study is to evaluate the rate of these polymorphisms in a group of patients from Central Anatolia. METHODS: Our study subjects consist of 65 men with histopathologically confirmed bladder TCC and 70 cancer-free control subjects. Restriction fragment length polymorphism (RFLP) method was used for the detection of polymorphisms of GSTT1 and GSTM1. RESULTS: There was no association between bladder cancer and GSTM1 polymorphism (ORs = 0.64, 95% CI = 0.32-1.29), but the probability of bladder cancer in patients with GSTT1 null genotype (67.9%), was significantly higher from the probability of bladder cancer with GSTT1 normal genotype (43.0%) statistically (ORs = 2.8, 95% CI = 1.16-6.75). CONCLUSION: Polymorphisms of these genes have been assessed to evaluate the relative risk of various cancers. Our intention is to continue this study with larger series of bladder cancer patients in a group of Turkish population from Central Anatolia.

HLA-B51 subtypes in Turkish patients with Behçet's disease and their correlation with clinical manifestations.

Behçet's disease (BD) is a multisystemic inflammatory disease believed to be triggered by microbial or environmental factors on a genetic platform. Clinically, it may have an impact on many body systems, including the mucocutaneous, ocular, articular, vascular, and neurological systems. In this study, we aimed to determine the HLA-B51 subtypes and their correlations with the clinical findings of BD. Fifty-one patients with BD and 44 gender- and age-matched healthy subjects were included in this study. The HLA-B51 subtypes of all participants were determined, and the correlations of the clinical manifestations of the disease with the HLA-B51 subtypes were analyzed. HLA-B51 positivity was found to be significantly higher in the patient group (P < 0.001, RR = 15.20), which had significantly more frequent HLA-B5101, HLA-B5102(01), HLA-B5109, and HLA-B5122 subtypes than the healthy subjects (all P < 0.05). Furthermore, considering the correlation between the genetic makeup and clinical findings, the HLA-B5109 subtype was found to be less frequent in patients with papulopustular skin lesions (P = 0.042). The frequency of HLA-B5103 was significantly higher in patients with central nervous system involvement (P = 0.015). There may be a relationship between HLA-B5102(01), HLA-B5109, and HLA-B5122 in addition to HLA-B51 and HLA-B5101(01) in Turkish patients with BD. The HLA-B5109 subtype can be protective against papulopustular lesion development; however, the HLA-B5103 subtype may pose a risk for neuro-Behçet development in BD.

Increased frequency of MEFV gene mutations in patients with primary dysmenorrhea.

OBJECTIVES: Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent attacks of fever and polyserositis and an autosomal recessive inheritance mode. Up to 15 % of FMF patients are reported to experience perimenstrual attacks. Primary dysmenorrhea could be an incomplete abdominal attack, or patients with dysmenorrhea may have increased frequency of MEFV gene mutation carriage. Therefore, we aimed to evaluate the frequency of MEFV gene mutations in patients with dysmenorrhea. METHODS: Eighty-four patients with primary dysmenorrhea attending consecutively to our gynecology department and 73 healthy female controls selected from hospital staff were included in the study, and MEFV gene mutations were analyzed. RESULTS: The prevalence of total allelic variants was significantly increased in dysmenorrhea patients (p = 0.015); analysis of individual variant rates revealed a significant increase in the frequency of MEFV gene mutations in dysmenorrhea patients compared with the control group (p = 0.036). CONCLUSION: Gynecologists and primary care physicians must be aware of FMF in the differential diagnosis of dysmenorrhea.

Frequency of alterations in the MEFV gene and clinical signs in familial Mediterranean fever in Central Anatolia, Turkey.

Familial Mediterranean fever is a recessive autoinflammatory disease that is frequent in Armenians, Jews, Arabs, and Turks. The MEFV gene is responsible for this disease. We looked for MEFV gene variations (polymorphism and mutations) in a population that resides in Central Anatolia, Turkey. DNA was extracted from peripheral blood leukocytes of 802 familial Mediterranean fever patients. The DNA sequence data were examined for approximately 150 different mutations and polymorphisms, including single nucleotide polymorphisms in different exons of the MEFV gene. The male:female ratio of these patients was 1.44:1. Mutations were detected in 48.1% of the patients; 7.5% were homozygous, 11.1% were compound heterozygous and 31.5% had only one identifiable mutant allele. No mutations were detected in 51.9% of the patients. The main clinical characteristics of the patients were: abdominal pain in 20.6%, arthritis in 22.9% and amyloidosis in 4.6%. Sixty-six percent of patients had a family history of familial Mediterranean fever; 19.4% of the patients were found to have parental consanguinity. We conclude that the genetics of familial Mediterranean fever is more complex than has previously been reported; heterozygous patients presenting a severe phenotype should be further analyzed for less common secondary MEFV mutations, using gene sequencing.

The azoospermia factor locus-c region was found to be related to Klinefelter syndrome in Turkish patients.

We looked for a possible association between Klinefelter syndrome (KFS) and microdeletions in the Y chromosome in Turkish KFS patients. We examined the frequency of KFS in male patients with proven non-obstructive azoospermia and the types of Y chromosome microdeletions in these KFS patients. Fifty azoospermic patients and 50 fertile men were included in this study. KFS was found in 14 azoospermic patients. Y chromosome microdeletions were found in eight KFS patients. Azoospermia factor locus c (AZFc) was the most commonly deleted interval in KFS patients. All KFS patients had elevated plasma follicle-stimulating hormone and luteinizing hormone concentrations, but they had normal plasma testosterone concentrations. Testis biopsy of five samples with Y microdeletions revealed Sertoli cell-only syndrome. No Y microdeletions were found in the fertile group. We concluded that there could be an association between the AZFc region and KFS. Screening for this should be part of diagnostic work-up, particularly in those considering assisted reproduction.

Genetic anomalies in patients with severe oligozoospermia and azoospermia in eastern Turkey: a prospective study.

Infertility is defined as the inability to conceive a child after one year of regular unprotected intercourse; it is a major health problem affecting about 10-15% of all couples. Infertility is due to a male factor in approximately 50% of cases. The human Y chromosome contains genes necessary for gonadal differentiation into a testis and genes for complete spermatogenesis. We examined the frequency and type of both chromosomal abnormalities and Y chromosome microdeletions in 90 patients with severe male factor infertility and 75 fertile control men. Thirty of the infertile patients had nonobstructive azoospermia, 30 had oligozoospermia and 30 had normozoospermia. Five of 30 were azoospermic, four of 30 were oligozoospermic and two of 30 were normozoospermic with Y chromosome microdeletions. The AZFc locus was the most frequently deleted region (64%). Ten cases with azoospermia, four cases with oligozoospermia and four cases with normozoospermia had chromosomal abnormalities. The 75 men with proven fertility were genetically normal. We conclude that various chromosomal abnormalities and deletions of the Y chromosome can cause infertility; therefore, genetic screening is indicated for infertile patients.