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.

ErbB receptor tyrosine kinase family expression levels in urothelial bladder carcinoma.

ErbB receptor tyrosine kinases family plays an important role in cell cycle regulation. Overexpression of ErbB receptors has been described in several solid tumors. The aim of this study was to investigate the levels of ErbB1, ErbB2, ErbB3, and ErbB4 expression in bladder cancer. Urinary bladder tumor samples were obtained from 33 bladder cancers and 7 non-cancerous bladder biopsies. The levels of ErbB1, ErbB2, ErbB3, and ErbB4 genes expression in bladder cancer were determined by real-time PCR. The presence of protein was confirmed by immunostaining. Expression of ErbB1, ErbB2, ErbB3, and ErbB4 genes increased 0.67, 4.72, 2.89, and 2.65-fold, respectively, in bladder tumors as compared with normal tissue. There was a significant difference between immunostaining results of ErbB4 protein in bladder tumors and normal bladder tissue (P<0.01). The present data suggest that ErbB2, ErbB3, and ErbB4 genes may have a role in bladder cancer tumorigenesis.

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.

Interaction between periodontal disease and systemic secondary amyloidosis: from inflammation to amyloidosis.

BACKGROUND: It has become increasingly clear in recent years that periodontal disease can cause a dramatic increase in the levels of markers of systemic inflammation, and that periodontal treatment can result in reduction in the levels of these markers. We have previously shown that the prevalence of moderate to severe periodontitis was significantly higher in patients with familial Mediterranean fever (FMF) with amyloidosis than in patients with FMF without amyloidosis. Thus, the aim of this study is to investigate if chronic periodontitis is associated with secondary amyloidosis in the Black Sea region of Turkey. METHODS: A total of 112 patients with biopsy-proven secondary amyloidosis (59 patients with FMF, 40 patients who were either chronically infected or had malignant disease, 13 patients with periodontitis) and 22 healthy subjects, were included in this study. Periodontal health and disease were evaluated using gingival index (GI), papillary bleeding index (PBI), plaque index (PI), and periodontal disease index (PDI). The concentrations of serum acute phase reactants (APRs) were measured at baseline and at 4 to 6 weeks after completion of the non-surgical periodontal therapy. RESULTS: The prevalence of moderate to severe periodontitis was 47.5% in patients with FMF, 72.5% in patients who were either chronically infected or had malignant disease, and 84.6% in patients with periodontitis. Serum levels of APRs in patients with amyloidosis were reduced significantly after non-surgical periodontal therapy (P <0.01). CONCLUSIONS: Periodontitis can increase the levels of APRs and potentiate the development of amyloidosis either by themselves or association with traditional factors, such as FMF and other chronic inflammatory diseases. Thus, preventing or treating periodontitis might prevent or at least alleviate the progression of amyloidosis. Periodontal evaluation should be performed as part of a medical assessment and considered as an etiologic factor for secondary amyloidosis.

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.

Polymorphisms of the serotonin-2A receptor and catechol-O-methyltransferase genes: a study on fibromyalgia susceptibility.

Genetic and environmental factors are thought to play roles in the etiopathology of fibromyalgia syndrome (FMS). The objective of this study was to determine the potential effects of single nucleotide polymorphisms (SNPs) in catechol-O-methyltransferase (COMT) (rs4680) and 5-hydroxytryptamine (serotonin) 2A (5-HT2A) receptor (rs6313 and rs6311) genes on susceptibility to FMS. One hundred seventy-one women (80 FMS, 91 control) were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for the genotyping analyses. Genotype and allele frequencies were calculated by the chi-square test. Beck depression inventory, state and trait anxiety inventory and symptom checklist-90 revised (SCL-90-R) tests were applied to both patients and controls. There were no observed differences in the frequencies of alleles and genotypes between patients and controls for the COMT, and the two 5-HT2A receptor gene polymorphisms (P>0.05). Our results suggest that the investigated polymorphisms seem not to be the susceptibility factors in etiology of FMS.

MEFV mutations in patients with familial Mediterranean fever in the Black Sea region of Turkey: Samsun experience [corrected].

OBJECTIVE: To investigate MEFV mutations among patients with familial Mediterranean fever (FMF), their relatives, and healthy controls in the Black Sea region of Turkey; to compare 3 different MEFV mutation analysis methods; to evaluate the role of MEFV mutations in the diagnosis of FMF; and to investigate the role of M694V in the development of amyloidosis. METHODS: In total, 890 subjects (625 patients, 165 relatives, 100 healthy controls) were included in this prospective study. MEFV mutations were studied with the amplification refractory mutation system (ARMS; n = 335), polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP; n = 335), and reverse hybridization assay (FMF StripAssay; n = 693). RESULTS: All methods were used in 79 patients. The ratio of false negativity was about 2% using ARMS compared to PCR-RFLP. The FMF StripAssay was used to investigate 9 more mutations and detected 17 mutations in 14 patients. The M694V/M694V genotype was more common in patients with amyloidosis (37%) compared to patients without amyloidosis (18%) (p = 0.009). The frequency of MEFV carriers was 27%. The frequency of individuals having 2 mutations among asymptomatic relatives of FMF patients was 6%. CONCLUSION: The FMF StripAssay is a reliable and time-saving method. In spite of detection of new mutations and developments in MEFV assay technology, there were patients in whom no mutation was detected. Our data, combined with previous studies, show that patients having M694V/M694V carry a risk for amyloidosis.

Prostate-specific antigen and 17-hydroxylase polymorphic genotypes in patients with prostate cancer and benign prostatic hyperplasia.

We investigated the association of prostate cancer (PCa) and benign prostatic hyperplasia (BPH) with genetic polymorphisms in prostate-specific antigen (PSA) (-158 G/A) and 17-hydroxylase (CYP17) (-34 T/C) genes in a Turkish population. In this study, we investigated the distribution of these polymorphisms in 148 PCa patients, 136 BPH patients, and 102 healthy individuals as controls. The polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism assay. Genotype and allele frequencies were calculated, and their associations with PCa or BPH risk are assayed. The frequency of PSA gene GA and GG genotypes was significantly higher in PCa patients than in controls (p = 0.017 and p = 0.019, respectively). GG genotype was also associated with BPH (p = 0.033). In a case analysis, according to Gleason score, the association of PSA gene GG genotype with Gleason score >7 was near to statistical significance (odds ratio, 2.94; 95% confidence interval, 0.95-9.28). There was also an association between CYP17 polymorphism and BPH (p = 0.004). No association was observed between PCa and CYP17 gene polymorphism. These data demonstrate that PSA gene promoter variation may play a significant role in the development of PCa and BPH, and that CYP17 gene polymorphism may be associated with BPH in the Turkish population studied.

Association of serotonin 2A receptor and lack of association of CYP1A2 gene polymorphism with tardive dyskinesia in a Turkish population.

The aim of this study was to investigate the possible association of serotonin 2A receptor gene (HTR2A) -1438 G/A polymorphism and CYP1A2 gene 163C/A polymorphism with tardive dyskinesia (TD) in a Turkish population. A total of 47 patients with persistent TD, 80 patients who were consistently without TD, and 100 healthy controls were included in this study. The polymorphic regions of -1438 G/A polymorphism of HTR2A receptor gene (rs6311) and 163C/A of CYP1A2 (rs762551) gene were amplified using polymerase chain reaction (PCR), followed by digestion with restriction enzymes MspI and Bsp1201. Genotype and allele frequencies were calculated by the chi(2)-test. Crude and adjusted odds ratios (ORs) were estimated, and 95% confidence intervals (CIs) were computed by multivariate logistic regression analysis. The genotype and allele frequencies of HTR2A and CYP1A2 gene were similar in schizophrenia with TD, schizophrenia without TD, and healthy controls. The logistic regression analysis showed that cumulative exposure to antipsychotic drugs for every year (p = 0.003; OR = 1.15; CI = 1.07-1.23), and AA genotype of HTR2A gene (p = 0.0258; OR = 4.34; CI = 1.19-15.81) are risk factors for TD. The same logistic regression model showed no association between CYP1A2 polymorphism and TD. The results of the present study seem to indicate that HTR2A gene polymorphism influences the tendency to express TD following prolonged antipsychotic drug exposure in Turkish schizophrenia patients.

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.