Korkut Ulucan

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.

Non-alcoholic fatty liver disease in obese children and the relationship between metabolic syndrome criteria.

AIM To investigate metabolic syndrome (MetS) and MetS criteria, and to establish whether metabolic syndrome criteria were associated with non-alcoholic fatty liver disease (NAFLD) in obese children. METHODS A total of 451 pubertal obese children (8-18 years old) were enrolled in the study. Patients were divided into three groups according to the degree of steatosis. Antropometric and laboratory measurements of the participants were recorded. RESULTS Of 451 obese children, 217 (48.1%) were diagnosed as having NAFLD and 96 (21.3%) as having MetS. The frequency of abdominal obesity, hypertension, impaired fasting glucose, hyperinsulinemia, dyslipidemia and type 2 diabetes mellitus (T2DM) were 61.8% (279), 25.7% (116), 4.4% (20), 54.3% (245), 41% (185) and 2.2% (10), respectively. The prevalence of NAFLD among patients with MetS [73% (70/96)], was significantly higher than the frequency of hypertension [55% (53/96)] and abnormalities of glucose metabolism [23% (22/96)], but almost equal to the frequency of dyslipidemia [78% (75/96)]. The prevalence of MetS criteria were higher in patients with NAFLD than those without NAFLD. Except impaired fasting glucose, blood pressure and T2DM significant difference was found between groups for all. It was observed that the number of MetS criteria increased in parallel with the severity of steatosis. CONCLUSION NAFLD in obese children is strongly associated with multiple MetS criteria. In addition to NAFLD is not only a liver disease, but also early mediator that reflects metabolic disorder, and liver ultrasound can be a useful tool for MetS screening.

Effects of ACE inhibitors on insulin resistance and lipid profile in children with metabolic syndrome.

Objective: The aim of this study was to evaluate the effects of using ACE inhibitors on insulin resistance, glucose metabolism, body fat composition, and lipid profile in children over 10 years of age with obesity-associated metabolic syndrome (MS). Methods: A total of 53 children with MS, who had been followed for at least one year were included in the study. The sample was divided into two groups: Group 1-30 obese children (13 female, 17 male) who were not using an ACE inhibitor and Group 2-23 obese children (13 female, 10 male) who were using an ACE inhibitor. Anthropometric and laboratory dataobtained at baseline and at the 3rd, 6th, and 12th months of follow-up were compared in the two groups. Results: Comparison of the data in the two groups at 3rd, 6th, and 12th months revealed no statistically significant differences in terms of weight standard deviation score (SDS), body mass index SDS, weight for height percentile, body fat percentage, and very low-density lipoprotein (VLDL)values. However, there were statistically significant differences in mean glucose and insulin levels, homeostasis model assessment for insulin resistance, LDL and high-density lipoprotein values, and highly significant differences in mean triglyceride values. Conclusions: The positive effects of ACE inhibitor drugs, particularly on hypertriglyceridemia and insulin resistance, might bring them forth as first-line drugs in the treatment of obese and hypertensive children. Randomized, controlled, double-blind, and long-term studies are needed for a definitive conclusion. Conflict of interest:None declared.

Transient Neonatal Diabetes Mellitus in a Turkish Patient with Three Novel Homozygous Variants in the ZFP57 Gene

Neonatal diabetes mellitus (NDM) is a rare form of diabetes that presents within the first six months of life. Nearly 70% of these cases have loss of methylation at the differentially methylated region on chromosome 6q24. To describe the findings in a Turkish male patient with NDM caused by a loss of methylation at chromosome 6q24 and three novel homozygous mutations in the ZFP57 gene, methylation-specific PCR was carried out at 6q24 and mutation analysis of ZFP57 gene was maintained by direct sequencing. Sequencing of ZFP57 gene revealed the hypomethylation of chromosome 6q24 and three novel mutations (chr6:29.641.413 A>T, 29.641.073 C>T, and 29.640.855 G>C), respectively. The latter mutation seems to display the patient’s condition due to a highly conservative amino acid substitution in the protein. We suggest the ZFP57 gene as a causative factor for NDM and it should be considered in genetic testing. Further studies including functional analysis of the detected mutations will provide precise information regarding the effect of the mutations. Conflict of interest:None declared.

Analysis of Solute Carrier Family 6 Member 4 Gene promoter polymorphism in young Turkish basketball players.

The serotonin transporter (5-hydroxytryptamine transporter, 5- HTT) gene (SLC6A4) is considered to be one of the most important candidate genes for genetic involvement in psychiatric conditions like anxiety, self- confidence and motivation. In the present study, we aimed to analyze the distribution of SLC6A4 promoter long and short (L and S, respectively) polymorphism in young Turkish basketball players. We enrolled 24 players in the study, 17 were female and 7 were male. 12 %, 35 % and 53 % of the females had SS, LS and LL genotype, respectively; whereas %28,5 of the males had SS and the same percentage of them had LS, and % 43 had LL genotype. When we examine the allelic counts, L allele was recorded as 71% in females and 57% in males; S allele was 29% in females and 43% in males. Our results were in agreement with the previous ones, indicating the presence of L allele in individuals dealing with sport. We suggest that SLC6A4 promoter analysis is important for genetic counseling for the individuals who are prone to be successful in sports.

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.

Distribution of Angiotensin-1 Converting Enzyme Insertion/Deletion and α-Actinin-3 Codon 577 Polymorphisms in Turkish Male Soccer Players.

Angiotensin-1 converting enzyme (ACE) gene and α-actinin-3 (ACTN3) gene polymorphisms are considered to be the most important candidate genes for genetic predisposition to human athletic performance. In the present study, we aimed to analyze the distribution of ACE and ACTN3 polymorphisms for the first time in male Turkish soccer players. In this prospective study, our cohort consisted of 25 professional players, all with Turkish ancestry. Polymerase chain reaction (PCR)-restriction length polymorphism was used for the characterization of the genotype of ACTN3 and single PCR for ACE. For ACE genotype, 16%, 44%, and 40% of the players had insertion/insertion (II), insertion/deletion (ID), and deletion/deletion (DD) genotypes, respectively, whereas 20% had XX, 36% had RX, and 44% had RR genotypes for ACTN3. When we examined the allelic percentages, for ACE, D allele was recorded as 62 and I as 38, and for ACTN3, R allele was 62 and X was 38. Our results were in agreement with the previous reports, indicating the presence of ACTN3 D and ACE X allele in soccer players. We suggest that ACE and ACTN3 genotypes are important biomarkers for genetic counseling for the individuals who are prone to be successful soccer players.

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.

Effect of Cytokine Signaling 3 Gene Polymorphisms in Childhood Obesity.

Objective: Although polymorphisms in suppressor of cytokine signaling 3 (SOCS3) was reported to be related to obesity, Metabolic syndrome (MS), and type 2 diabetes mellitus in various adult studies, there is a lack of data in children. In this study, we examined eight reported polymorphisms of SOCS3 in obese Turkish children and adolescent with and without MS and compared the results with that of controls. Methods: One hundred and forty eight obese and 63 age- and sex-matched control subjects were enrolled in the study. Obesity classification was carried out according to body mass index. World Health Organization and National Cholesterol Education Program criteria were used for the diagnosis of MS. Genotyping procedure was carried out by polymerase chain reaction and Sanger sequencing protocol. Results: The frequency of rs2280148 polymorphism was significantly higher in obese subjects with MS than in the control group, whereas the frequency of rs8064821 polymorphism was significantly higher in obese subjects with MS than in obese children without MS. Conclusion: The significant associations of certain SOCS3 polymorphisms with obesity parameters in both MS and MS -related insulin resistance, hypertension, and fatty liver suggest that polymorphisms in this gene may play a role in the pathogenesis of MS and also that they can be potentially used as a marker for attenuated or aggressive disease.

Genetics of Trichotillomania

1 Üsküdar Üniversitesi, Mühendislik ve Doğa Bilimleri Fakültesi, Moleküler biyoloji ve Genetik Bölümü, İstanbul, Türkiye 2 Marmara Üniversitesi, Diş Hekimliği Fakültesi, Tıbbi biyoloji ve Genetik Bölümü, İstanbul, Türkiye * Sorumlu Yazar: Korkut Ulucan1,2, MSc, PhD. Haluk Türksoy Sok. No:14, Altunizade, Üsküdar, Istanbul,Türkiye, 34662 Uskudar–IstanbulTurkey E-mail: korkutulucan@hotmail.com Phone:W: +9021640022222409, F :+902164741256, M: +905326921922 Özet Trikotillomani (saç ve kıl koparma hastalığı) kişide devamlı saç yolumunun gözlemlendiği bir psikiyatrik bozukluk olarak tanımlanabilir. Bu durumun nörobiyolojisi net olarak bilinmemektedir. Bu nedenden dolayı tedavisi içinde kesin çözümler sunulamamaktadır. Molekğler genetik çalışmaları trikotillomaninin etiyolojisinin daha iyi anlaşılması ve bu bozukluğun tedavi edilmesi için büyük önem taşımaktadır. Günümüze kadar yapılan çalışmalar ile trikotillomani hakkında eldeki bilgiler kısıtlıdır. Yapılan moleküler analizler HOXB8, SAPAP3, DRD1, DRD4, SLC6A4 genlerinin hastalık ile ilişkili olabildiğine dair ipuçları vermektedir. Bu derlemede trikotillomaninin psikolojik ve fizyolojik temelleri ve sınıflandırılışı ve ardından da trikotillomaniye dair moleküler genetik çalışmalar, hayvan çalışmaları ve bozukluk ile ilişkili olduğu düşünülen genetik polimorfizmler anlatılacaktır. Eldeki bilgilerin derlendiği bu makalenin sonrasında gerçekleştirilebilecek olan moleküler çalışmalara da yön vereceğini ümit etmekteyiz. Anahtar Kelimeler: psikiyatri, genetik, polimorfizm Abstract Trichotillomania can be described as a psychiatric disorder where a recurring hair pulling behaviour is observed in an individual. Neurobiological causes of this condition is still unclear. Because of this, definite solutions can not be presented in the treatment. Molecular genetic studies are of great importance for a better understanding of the etiology of trichotillomania and for the treatment of this disorder. As of today, our knowledge and information about trichotillomania is limited. The molecular analyzes made suggest that HOXB8, SAPAP3, DRD1, DRD4, SLC6A4 genes may be related to the disease. In this review, the psychological and physiological basis and classification of trichotillomania will be followed by genetic polymorphisms that are thought to be related to molecular genetic studies, animal studies and disorders of trichotillomania. We hope that this article will also guide to the further molecular studies that can be carried out in this subject.