Ahmet Ilter Güney

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.

Autosomal Recessive Idiopathic Epilepsy in an Inbred Family from Turkey : Identification of a Putative Locus on Chromosome 9q32-33

Summary:  Purpose: The study describes the clinical features of an inbred family from Turkey with three members affected by seizures and tests possible autosomal recessive (AR) inheritance by means of linkage analysis.

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 alpha-actinin-3 gene on trained and untrained Turkish middle-school children’s sprinting performance: a pilot study

ACTN3 R577X polymorphism was evaluated in trained and untrained Turkish middle-school children’s sprinting performance. Twenty trained and 30 untrained children were genotyped; the frequencies of RR, RX and XX genotypes were 65, 30 and 5% in the trained individuals and 50, 27 and 23% in the controls (untrained), respectively. The R allele was present in 80% of the trained and 63% of the untrained individuals, whereas the X allele was present in 20% of the trained and 37% of the untrained individuals. The average values of time taken for running 50 m for the trained and untrained groups were 10.21 ± 0.68 and 11.88 ± 1.18 s in RR genotypes, and 10.48 ± 0.54 and 12.28 ± 1.26 s in RX genotypes, respectively. These differences were statistically significant and ecologically meaningful. Such polymorphism may form an informative criterion for identifying individuals who might become talented sprinters with suitable training.

Transforming growth factor-β3 intron 5 polymorphism as a screening marker for non-syndromic cleft lip with or without cleft palate.

In this study, we evaluated the effect of transforming growth factor β3 intron 5 position +104 A➝G (TGF-β3 IVS5+104AG) transition in patients with a non-syndromic cleft lip with or without cleft palate (NSCL/P). A total of 68 patients and 114 controls were recruited for the study. A genotyping procedure was carried out using the PCR-RFLP method. For statistical analysis, the Chi-square test was used to compare data between the patient and control groups. The frequencies of the AA, AG and GG genotypes were 24, 29 and 47%, respectively, for the patients and 54, 36 and 10%, respectively, for the control group. The GG genotype and G allele were significantly different in the patient group compared with the control (p=0.0001). We conclude that SfaN1 polymorphism in TGF-β3 may be a good screening marker for the prediction of NSCL/P in patients. However, more studies with extended sample numbers should be carried out to clarify the effect of the examined gene region on NSCL/P.

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.