Deniz Kirac

Detection of Mitochondrial DNA Mutations in Nonmuscle Invasive Bladder Cancer

BACKGROUND Mitochondrial DNA (mtDNA) mutations have been recently described in various tumors; however, data focusing on bladder cancer are scarce. To understand the significance of mtDNA mutations in bladder cancer development, we investigated the mtDNA alterations in bladder cancer cases. METHODS We studied the mtDNA in 38 bladder tumors and 21 microdissected normal bladder tissue samples. Mitochondrial genes ATPase6, CytB, ND1, and D310 region were amplified by polymerase chain reaction and then sequenced. RESULTS We detected 40 mutations in our patient population. Our findings indicate that G8697A, G14905A, C15452A, and A15607G mutations are frequent in bladder cancers (p<0.05). In addition, the incidence of A3480G, T4216C, T14798C, and G9055A mutations were higher in patients with bladder tumors. CONCLUSIONS In conclusion, the high incidence of mtDNA mutations in bladder cancer suggests that mitochondria could play an important role in carcinogenesis and mtDNA could be a valuable marker for early bladder cancer diagnosis.

The frequency and the effects of 21-hydroxylase gene defects in congenital adrenal hyperplasia patients.

Congenital adrenal hyperplasia (CAH) is a group of genetic endocrine disorders, caused by enzyme deficiencies in the conversion of cholesterol to cortisol. More than 90% of the cases have 21‐hydroxylase deficiency (21‐OHD). The clinical phenotype of the disease is classified as classic, the severe form, and nonclassic, the mild form. In this study, it was planned to characterize the mutations that cause 21‐OHD in Turkish CAH patients by direct sequencing and multiplex ligation‐dependent probe amplification (MLPA) analysis and to investigate the type of CAH (classic or nonclassic type) that these mutations cause. A total of 124 CAH patients with 21‐OHD and 100 healthy volunteers were recruited to the study. Most of the mutations were detected by direct sequencing. Large gene deletions/duplications/conversions were investigated with MLPA analysis. Results were evaluated statistically. At the end of our study, 66 different variations were detected including SNPs and deletions/duplications/conversions. Of these variations, 18 are novel, of which three cause amino acid substitutions. In addition, 15 SNPs which cause amino acid changes were identified among these variations. If similar results are obtained in different populations, these mutations, in particular the novel mutation 711 G>A, may be used as markers for prenatal diagnosis.

Effect of high-fat intake on motor activity, homovanillic acid and 5-hydroxyindoleacetic acid levels in striatum and cortex of rats exposed to stress.

Abstract The aim of the present study was to investigate whether high fat consumption changes the effects of stress on both motor activity performance, striatal and cortical dopamine and serotonin metabolites in rats. The animals were fed either with high fat or standard diet for 4 weeks. Restraint stress lasting for 15 min at +4°C was applied daily to stress-exposed groups. Motor activity performance was measured weekly by using motor activity monitoring systems. At the end of the study, homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) levels of the striatum and cerebral cortex were measured by HPLCEC. It was observed that restraint stress increased locomotor activity and high-fat diet prevented this effect. Stress and high-fat intake had an additive decreasing effect on striatal HVA levels. 5-HIAA levels, on the other hand, were lower in both high fat and high fat + stress groups compared to the stress group. These results suggest that high-fat intake differentially affected the stress response on striatal dopaminergic and serotonergic neurons in rat brain regions studied and this may be related to the effects observed in motor activity performance.

Role of Peroxisome Proliferator Activated Receptor Alpha (PPARA) rs4253778 Polymorphism in Endurance Phenotype

An individual’s athletic performance is determined with the intersection of the genetic endowment that he/she owns, and its interaction with environmental factors such as training, nutrition, mentoring and sleeping[1]. Around 70% of the variance in athletic performance is explained by genetic factors. Environmental factors play crucial roles in effecting the expression of several genes; and all of these subjects are examined under the topic of epigenetics. As of today, a total of 250 genes are considered to have effect on human performance, and the number seems to increase as we have the new molecular high-through put techniques that are introduced to molecular genetics, it is now possible to analyse hundreds of SNPs in only on application. The need for identifying genetic variants contributing to athletic performance has been challenging because of the possible involving of the examined genes that are considered to have a minor phenotypic effect. But when we consider the total effect of these genetic variant, a huge contribution is apparent, and to have information on these variants, we will have a chance to speculate on the cumulative effect of these variants on athletic performance[2]. One of the important markers of these variants is peroxisome proliferator activated receptor alpha (PPARA) intron 7G/C polymorphism (rs4253778). The PPARA is located on chromosome 22 (22q12-q13.1). PPARs are members of the nuclear hormone receptor super family and PPARA codes for transcriptional factor named nuclear receptor protein peroxisome proliferator activated receptor alpha (PPAR-alpha)[3]. PPARA gene has been Role of Peroxisome Proliferator Activated Receptor Alpha (PPARA) rs4253778 Polymorphism in Endurance Phenotype

Effects of MC4R, FTO, and NMB gene variants to obesity, physical activity, and eating behavior phenotypes

Obesity is a major contributory factor of morbidity and mortality. It has been suggested that biological systems may be involved in the tendency to be and to remain physically inactive also behaviors such as food and beverage preferences and nutrient intake may at least partially genetically determined. Consequently, besides environment, genetic factors may also contribute to the level of physical activity and eating behaviors thus effect obesity. Therefore the aim of this study is to investigate the effect of various gene mutations on obesity, physical activity levels and eating behavior phenotypes. One hundred patients and 100 controls were enrolled to the study. Physical activity levels were measured with an actical acceloremeter device. Eating behaviors were evaluated using Three‐Factor Eating questionnaire (TFEQ). Associations between eating behavior scores and physical characteristics were also evaluated. The information about other obesity risk factors were also collected. Mutations were investigated with PCR, direct sequencing and Real‐Time PCR. rs1051168, rs8050146 −2778C > T mutations were found statistically significant in patients, rs1121980 was found statistically significant in controls. 21 mutations were found in MC4R and near MC4R of which 18 of them are novel and 8 of them cause amino acid change. In addition, it was found that, some obesity related factors and questions of TFEQ are associated with various investigated gene mutations. Any relation between gene mutations and physical activity levels were not detected. It is thought that, due to the genotype data and eating behaviors, it may be possible to recommend patients for proper eating patterns to prevent obesity.

Congenital Hyperinsulinism and Cardiomyopathy

We read with great interest the article by Bulbul et al [1] appearing in Volume 29, Issue 3, 2010.They presented a babywith hypertrophic cardiomyopathy and hyperinsulinemic hypoglycemia resistant tomedical treatment.Themutation analysis could not been performed in this case, however the disease clearly was due to an ATP-sensitivepotassium (KATP) channel gene mutation (either SUR1 or Kir6.2) in the pancreatic beta cells.The authors hypothesized that both the pancreatic and cardiac KATP channel might be affected. Both of these are structurally similar, though genes encoding these channels are different [2, 3]. It seems unreasonable to carry both cardiac and pancreatic KATPmutations for the presented case. In addition, KATP channel inhibition in cardiac muscle cells will result in dilated cardiomyopathy rather than hypertrophic [4]. Cardiomyopathy and dysrhythmia in this case could not be due to cardiac KATP inhibition for these reasons. I suggest that the cardiac problems resulted from severe hyperinsulinism itself.