Hasan Bagci

Polymorphisms of CYP1A1, GSTM1, GSTT1, and Prostate Cancer Risk in Turkish Population

Prostate cancer is the most common cancer among men in many countries. Although the etiology of prostate cancer largely is unknown, both genetic and environmental factors may be involved. Advanced age, androgen metabolism, and heredity-race have been reported to be possible risk factors. On the other hand, several studies indicate that genetic polymorphisms in biotransformation enzymes play a role in prostate cancer development. In this study, association of the prostate cancer risk with genotype frequencies of the Phase I (CYP1A1) and Phase II (GSTM1 and GSTT1) biotransformation enzymes was investigated in 321 Turkish individuals (152 prostate cancer patients and 169 age-matched male controls). The presence or absences of the GSTM1 and GSTT1 genes were determined by a PCR-based method. Genotypes of CYP1A1 were determined by MspI-RFLP. The prevalence of GSTM1 null genotype in the cases was 64 percent, compared to 31 percent in the control group, indicating a strong association (OR = 4.08, 95%CI = 2.50–6.69). No association was observed between either GSTT1 null genotype or CYP1A1 polymorphism and prostate cancer incidence. No statistically significant association was observed between smoking status of the patients and any of the polymorphisms studied. In conclusion, results of this study indicate that only the GSTM1 null genotype may play an important role as a risk factor for prostate cancer development in Turkish population.

Vitamin D receptor gene polymorphisms in patients with urolithiasis

Urolithiasis is a multifactorial disease, the onset and severity of which is influenced by both genetic and environmental factors. This study represents an investigation of the role of vitamin D receptor (VDR) gene polymorphisms (ApaI, BsmI, and TaqI) and combined genotypes in urolithiasis in a Turkish population. We studied 110 patients with urinary stones and 150 control subjects. The polymorphic regions were amplified using polymerase chain reaction, followed by digestion with restriction enzymes BsmI, ApaI, and TaqI, and analyzed electrophoretically. Genotype and allele frequencies were calculated, and the association with urolithiasis, family history, and recurrence of stone was investigated. Our data provide no evidence for an association between urolithiasis and VDR ApaI, BsmI, and TaqI genotypes. We also analyzed the effects of VDR ApaI, BsmI, and TaqI genotypes in combination; the “GTT” VDR haplotype, constructed from three adjacent restriction fragment length polymorphisms was overrepresented among the urolithiasis patients. However, no significant differences between heterozygous carriers (OR 1.302; 95% CI 0.527–3.215) and homozygous carriers (OR 3.39; 95% CI 0.719–15.985) were observed in our study population. A significant association was found only between the ApaI polymorphism and family history (P=0.017; χ2=5.657). Our data indicate that the VDR ApaI, BsmI, and TaqI polymorphisms do not confer a significant risk for urolithiasis.

P53 Codon 72 and HER2 Codon 655 Polymorphisms in Turkish Breast Cancer Patients

The polymorphisms in codon 72 of the tumor suppressor protein p53 (P53) gene and codon 655 of the human epidermal growth factor receptor 2 (HER2) gene have been suggested to play roles in most cancers. The purpose of this study was to investigate the association between common variants of HER-2 and P53 genes with breast cancer risk. Blood samples collected from 204 women with primary breast carcinoma and 192 healthy female controls were analyzed through polymerase chain reaction-restriction fragment length polymorphism methods. The frequencies of Arg/Arg, Arg/Pro, and Pro/Pro genotypes for P53 codon 72 were 51.7%, 41.4%, and 6.9% in patients and 42.6%, 47.3%, and 10.1% in controls, respectively. The frequencies of Ile/Ile, Ile/Val, and Val/Val genotypes for HER2 codon 655 were 75.0%, 22.5%, and 2.5% in patients and 73.4%, 25.0%, and 1.6% in controls, respectively. The genotype and allele frequencies between patient and control groups for P53 gene polymorphism were not significantly different (p = 0.177 and p = 0.07, respectively). Similarly, the genotype and allele frequencies between patient and control groups for HER2 gene polymorphism were not significantly different (p = 0.716 and p = 0.891, respectively). With the exception of association between the P53 codon 72 polymorphism and tumor stages (p = 0.026), there was no significant association between the studied polymorphisms and clinicopathological characteristics. The P53 gene codon 72 Arg/Pro and Her2 gene Ile655Val polymorphisms were not associated with the risk of breast cancer in Turkish women. However, significant associations between the P53 codon 72 and the homozygote and heterozygote Pro genotypes with tumor stages were found.

Clinical significance of MEFV mutations in ankylosing spondylitis.

OBJECTIVE The aim of the present study was to investigate the prevalence of MEFV gene mutations in patients with ankylosing spondylitis (AS) and to assess the clinical significance of the MEFV gene mutations in AS. METHODS Eighty AS patients and 85 healthy controls were examined for 12 common MEFV mutations via strip-assay technique. Bath ankylosing spondylitis disease activity index (BASDAI), bath ankylosing spondylitis functional index (BASFI), visual analogue scale (VAS) for pain, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Schober test, chest expansion measurements, hip involvement, ocular involvement, articular pain, and presence of syndesmophytes were used to assess the disease severity in patients. RESULTS Twenty-four of the AS patients (30%) and 17 of the healthy controls (20%) were found to carry a single MEFV mutation. There was no significant difference between the AS patients and controls in terms of MEFV gene mutation frequency (p = 0.13, OR: 1.71, 95% CI: 0.83-3.50). When the patients were divided into two groups as MEFV mutation carriers and noncarriers, there was significant difference between the groups regarding BASFI and BASDAI whereas there was no significant difference in VAS score for pain. No association was found with the clinical findings and MEFV mutation except hip involvement. While there was no significant difference in CRP levels, individuals with MEFV mutation had a higher ESR than the noncarriers. CONCLUSION MEFV gene mutation carriage rate was not found to be significantly higher in AS patients when compared with healthy controls. However having an MEFV mutation seems to aggravate the disease course in AS.

The relationship between the presence of ADHD and certain candidate gene polymorphisms in a Turkish sample.

Due to the high heritability of attention-deficit hyperactivity disorder (ADHD), parents of children with ADHD appear to represent a good sample group for investigating the genetics of the disorder. The aim of this study was to investigate the association between ADHD and six polymorphisms in five candidate genes [5-HT2A (rs6311), NET1 (rs2242447), COMT (rs4818), NTF3 (rs6332), SNAP-25 (rs3746544) and (rs1051312)]. We included 228 parents of children diagnosed with ADHD and 109 healthy parents as the control group. The polymorphisms were genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) assays and analyzed using the chi-square test and the multinomial logit model. SNAP-25 (rs3746544) polymorphism was associated with loading for ADHD, while 5-HT2A (rs6311) and NET1 (rs2242447) polymorphisms were associated with ADHD. On the other hand, there was no significant association between the SNAP-25 (rs1051312), NTF3 (rs6332), or COMT (rs4818) gene polymorphisms and ADHD. In addition, we found that even if variation in the SNAP-25 gene alone does not affect the phenotype, it may nevertheless lead to the emergence of a clinical ADHD picture in the presence of other genetic factors. Our findings suggest that a combination of NET1 (rs2242447) and SNAP-25 (rs3746544) is a risk factor for ADHD. Problems associated with the noradrenergic and serotonergic systems and SNAP-25 may play a role, both alone and in interaction with one another, in the pathophysiological mechanisms of ADHD.

SOX4 expression levels in urothelial bladder carcinoma

High levels of SOX4 gene expression have been reported in a variety of human cancers. The protein may function in the apoptosis pathway, leading to cell death as well as to tumorigenesis. The aim of this study was to investigate the levels of SOX4 expression in bladder cancer. Urinary bladder tumor samples were obtained from 57 bladder cancer and 13 normal bladder biopsies. The levels of SOX4 expression in bladder cancer were determined by immunohistochemistry and real-time PCR. SOX4 gene expression was increased 2.2 times in bladder tumors as compared with normal tissue. The presence of protein was confirmed by immunostaining. There were significant differences between immunostaining of bladder tumors and normal bladder tissue (P=0.001). The present data suggest that SOX4 gene may have a role in bladder cancer tumorigenesis.

Periodontal disease in patients with familial Mediterranean fever: from inflammation to amyloidosis

BACKGROUND AND OBJECTIVE Familial Mediterranean fever stimulates a very intense acute-phase reactants response and if left untreated eventually leads to amyloidosis. The aim of this study was to determine the prevalence of periodontal disease among patients with familial Mediterranean fever in the Black Sea region in Turkey and to evaluate whether periodontitis is related to amyloidosis in patients with familial Mediterranean fever. MATERIAL AND METHODS One-hundred and thirty three patients with familial Mediterranean fever and 50 healthy subjects were included in this study. Periodontal health and disease were evaluated using the gingival index, papillary bleeding index, plaque index and periodontal disease index. The concentrations of serum acute-phase reactants were measured at baseline and at 4-6 wk after completion of the nonsurgical periodontal therapy. Genetic testing for familial Mediterranean fever was performed using the familial Mediterranean fever StripAssay. Kidney biopsy was carried out on all proteinuric patients. RESULTS The prevalence of moderate to severe periodontitis in familial Mediterranean fever patients with amyloidosis (80.6%) was significantly greater (p < 0.01) than in familial Mediterranean fever patients without amyloidosis (38%) and in controls (20%). Serum levels of acute-phase reactants in familial Mediterranean fever patients were reduced significantly following nonsurgical periodontal therapy (p < 0.01). CONCLUSION Periodontal therapy seems to reduce the serum levels of acute-phase reactants in patients with familial Mediterranean fever. Therefore, treating periodontitis might help to alleviate the disease burden in patients with familial Mediterranean fever.

Lack of evidence for association between endothelial nitric oxide synthase gene polymorphism (glu298asp) with Behçet’s disease in the Turkish population

Endothelial nitric oxide synthase (eNOS) could be a candidate gene for Behçet’s disease (BD). This study investigated the relationship of the eNOS Glu298→Asp polymorphism with the presence and severity of BD in the Turkish population. Ninety-two patients with BD and 100 controls were studied. Analyses of Glu298Asp polymorphism in exon 7 of the eNOS gene were made by the polymerase chain reaction (PCR)-restriction fragment length polymorphism technique. The frequencies of the eNOS genotypes were similar for BD patients (GG:GT:TT=58.7%:38%:3.3%) and controls (59.2%:33.7%:7.1 %), P=0.335. No evidence of difference was found in the frequency of the T allele between BD patients (22.3%) and controls (24%), [OR=0.91, 95% CI (0.55–1.50), P=0.690]. Glu298→Asp polymorphism of the eNOS gene does not appear to be associated with the presence of BD in the Turkish population.

Association of the polymorphisms in promoter and intron regions of the interleukin-4 gene with chronic periodontitis in a Turkish population.

Objectives. The etiology of periodontitis is related to the interaction between micro-organisms and host responses. Host modifying factors, such as genetic predisposition, may increase the severity of periodontitis. Recent works have shown that the levels of cytokine expression are regulated by genetic polymorphisms, and that these variations can interfere with progression of the disease. This study therefore aimed to evaluate whether interleukin (IL) 4 gene polymorphisms are associated with severe generalized chronic periodontitis. Material and Methods. Seventy-five severe generalized chronic periodontitis patients and 73 healthy subjects were examined. Blood samples were taken and genomic DNA was amplified by polymerase chain reaction (PCR). Identification of 70 base-pair repeat polymorphisms in intron 2 and C→T polymorphisms at −590 position of the promoter region was performed through PCR-restriction fragment length polymorphism (RFLP). Results. No significant differences were found in the allele and genotype frequencies between the control and periodontitis group. Conclusion. The IL-4 polymorphisms were not related to severe generalized chronic periodontitis in a Turkish population.

Lack of association between the G-2548A polymorphism of the leptin gene and psoriasis in a Turkish population

Background   Psoriasis is a multifactorial disease in which genetic and inflammatory factors play important roles. Leptin is classified as a cytokine and plays an important role in the regulation of the T‐helper response. A common polymorphism in the promoter of the human leptin gene (G‐2548A) may have a role in the pathogenesis of psoriasis.