Methylene Tetrahydrofolate Reductase C677T Mutation and Left Ventricular Hypertrophy in Turkish Patients with Type 2 Diabetes Mellitus

( Hulya Yilmaz ),( Bedia Agachan ),( Arzu Ergen ),( Zeynep Ermis Karaalib ),( Turgay Isbir ) 생화학분자생물학회 2004 BMB Reports Vol.37 No.2

This study was designed to investigate, in the Turkish population, the association of methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism and left ventricular hypertrophy (LVH) in patients with type II diabetes mellitus. Our study included 249 patients with type II diabetes mellitus (102 men, 147 women) and 214 healthy volunteers as controls (91 men, 123 women). MTHFR C677T genotypes were determined by polymerase chain reaction, restriction fragment length polymorphism techniques. No differences were observed in the distribution of MTHFR genotypes or allele frequencies in the cases versus the controls. The frequency of the MTHFR-mutated allele (T) was 31.7% in the type II diabetes mellitus versus 31.1% of the controls. The homozygous mutation (T/T) in the MTHFR gene was identified in 12% of the type II diabetes mellitus versus 9.3% of the controls. Patients with the TT genotype showed a higher prevalence of LVH when compared to patients with the CC and CT genotypes (p = 0.01). The MTHFR gene C677T mutation may be a possible risk factor for the development of LVH in the type II diabetic patients

Angiotensin-I converting enzyme gene polymorphism in Turkish type 2 diabetic patients

H . Arzu Ergen,Husrev Hatemi,Bedia Agachan,Hakan Camlica,Turgay Isbir 생화학분자생물학회 2004 Experimental and molecular medicine Vol.36 No.4

Non-insulin dependent diabetes melitus is often associated with some complications such as nephropathy, retinopathy and neuropathy. Genes of the renin angiotensin system are potential candidate genes for diabetic complications. We investigated the relationship betwen angio-phism in type 2 diabetic patients with and with-out diabetic nephropathy. Seventy five patients (25 type 2 diabetic patients with nephropathy, 50 type 2 diabetic patients without nephropathy) and 37 healthy controls were studied. Gene polymorphism of ACE was determined by PCR (polymerase chain reaction) amplification using allele-spesific primers. The frequencies of ACE D, ID and II genoypes among the patients with type 2 diabetic patients were found 48%, 42%, 10% whereas in control subjects, 27%, 60%, ing DD genotype without nephropathy increased 1.77 fold than control subjects (P< 0.05). There is no significant corelation between diabetic nephropathy and ACE gene polymorphism. But we found that ACE DD genotype increased significantly in type 2 diabetic patients com-pared to control subjects (P< 0.05).

CK2 Enzyme Affinity Against c-myc^424-434 Substrate in Human Lung Cancer Tissue

Yaylim, Ilhan,Ozkan, Nazli Ezgi,Isitmangil, Turgut,Isitmangil, Gulbu,Turna, Akif,Isbir, Turgay Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.10

CK2 is a serine threonine kinase that participates in a variety of cellular processes with more than 300 defined substrates. This critical enzyme is known to be upregulated in cancers, but the role of this upregulation in carcinogenesis is not yet fully understood but c-myc, one of the defined CK2 substrates, is a well-known proto-oncogene that is normally essential in developmental process but is also involved in tumor development. We evaluated the optimal enzyme and substrate concentrations for CK2 activity in both neoplastic and non-neoplastic human lung tissues using the c-$myc^{424-434}$ peptide (EQKLISEEDL) as a substrate. The activities measured for the neoplastic tissue were 600-750 U/mg protein while those for the control tissue was in the range of 650-800 U/mg. $K_m$ value for c-myc peptide was determined as $0.33{\mu}M$ in non-neoplastic tissue and $0.18{\mu}M$ in neoplastic tissue. In this study, we did not observe an increased activity in the neoplastic tissue when compared with the non-neoplastic lung tissue, but we recorded two times higher affinity for c-$myc^{424-434}$ in cancer tissue. Considering the metabolic position of c-$myc^{424-434}$, our results suggest that phosphorylation by CK2 may be important in dimerization and thus it might affect the regulation of c-myc in cancer tissues.

Association of the Cylin D1 G870A Polymorphism with Laryngeal Cancer: Are they Really Related?

Verim, Aysegul,Ozkan, Nazli,Turan, Saime,Korkmaz, Gurbet,Cacina, Canan,Yaylim, Ilhan,Isbir, Turgay Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

Background: Cylin D1(CCDN1) is an important regulator of the cell cycle whose alterations are thought to be involved in cancer development. There have been many studies indicating CCDN1 amplification or over-expression in a variety of cancer types. In addition to gene amplification, the G870A polymorphism may be related with altered CCDN1 activity, and therefore with cancer development. This hypothesis has been tested in different cancer types but results have been contradictory. We therefore aimed to investigate any relationship between CCDN1 A870G genotypes and laryngeal squamous cell cancer development and progression. Materials and Methods: A total of 68 Turkish patients with primary laryngeal squamous cell cancer and 133 healthy controls were enrolled. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to determine the CCDN1 genotypes. Results: No significant association was detected between CCDN1 genotypes and laryngeal squamous cell cancer (LxSCCa) development. Similarly CCDN1 genotypes were not related to clinical parameters of Lx SCCa. However, there was a very significant association between CCDN1 G allele and presence of perineural invasion (p=0.003; OR: 1.464; CI% 1.073-1.999). CCDN1 G allele frequency was significantly higher in the individuals with perineural invasion (85.7%) when compared to those without (58.5%). The 2 patients who died of disease were both found to possess the GG genotype. Conclusions: These results pose a controversy in suggesting a protective role of the G allele against LxSCCa development and support the association of CCDN1 gene GG genotype with mortality in patients with LxSCCa.

Methylene Tetrahydrofolate Reductase C677T Mutation and Left Ventricular Hypertrophy in Turkish Patients with Type II Diabetes Mellitus

Yilmaz, Hulya,Agachan, Bedia,Ergen, Arzu,Karaalib, Zeynep Ermis,Isbir, Turgay Korean Society for Biochemistry and Molecular Biol 2004 Journal of biochemistry and molecular biology Vol.37 No.2

This study was designed to investigate, in the Turkish population, the association of methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism and left ventricular hypertrophy (LVH) in patients with type II diabetes mellitus. Our study included 249 patients with type II diabetes mellitus (102 men, 147 women) and 214 healthy volunteers as controls (91 men, 123 women). MTHFR C677T genotypes were determined by polymerase chain reaction, restriction fragment length polymorphism techniques. No differences were observed in the distribution of MTHFR genotypes or allele frequencies in the cases versus the controls. The frequency of the MTHFR-mutated allele (T) was 31.7% in the type II diabetes mellitus versus 31.1% of the controls. The homozygous mutation (T/T) in the MTHFR gene was identified in 12% of the type II diabetes mellitus versus 9.3% of the controls. Patients with the TT genotype showed a higher prevalence of LVH when compared to patients with the CC and CT genotypes (p = 0.01). The MTHFR gene C677T mutation may be a possible risk factor for the development of LVH in the type II diabetic patients.

Chemopreventive Effects of Hydatid Disease on Experimental Breast Cancer

Altun, Ahmet,Saraydin, Serpil Unver,Soylu, Sinan,Inan, Deniz Sahin,Yasti, Cinar,Ozdenkaya, Yasar,Koksal, Binnur,Duger, Cevdet,Isbir, Cemil,Turan, Mustafa Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.4

Breast cancer is one of the most common and letal cancers in all over the world. Since there have been significant improvements in treatment of breast cancer, there is still a big need for alternative approaches. In this study, we aimed to investigate protective role of hydatid disease against breast cancer. Twenty Wistar rats were divided into two groups of 10 rats each Group I (control) and Group II. In Group II intraperitoneal hydatidosis was performed. Then DMBA was applied to mammary tissues of all rats. Immunohistochemistry studies for Ki-67 and S-100 in the tumoral tissue sections of DMBA induced mammary tumor in rats were performed. TUNEL Assay was used to detect apoptotic cells of tumoral tissue. In vivo anticancer activity testing was carried out by preventing the tumorigenesis by DMBA in mammary tissue of rats. The expressions of the Ki-67 and S-100 protein decreased in rats who had Hydatid Disease (HD) (Group II), compared with the control rats (Group I). TUNEL positive cells were higher in rats with HD (Group II), compared with the control rats (Group I). In vivo studies showed that HD prevented the tumorigenesis by DMBA in mammary tissue of rats with 50 percent.In the light of the evidence the present study showed that HD may have chemopreventive effects on DMBA induced breast cancer.

Lack of Influence of the ACE1 Gene I/D Polymorphism on the Formation and Growth of Benign Uterine Leiomyoma in Turkish Patients

Gultekin, Guldal Inal,Yilmaz, Seda Gulec,Kahraman, Ozlem Timirci,Atasoy, Hande,Dalan, A. Burak,Attar, Rukset,Buyukoren, Ahmet,Ucunoglu, Nazli,Isbir, Turgay Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.3

Uterine leiomyomas (ULM), are benign tumors of the smooth muscle cells of the myometrium. They represent a common health problem and are estimated to be present in 30-70% of clinically reproductive women. Abnormal angiogenesis and vascular-related growth factors have been suggested to be associated with ULM growth. The angiotensin-I converting enzyme (ACE) is related with several tumors. The aim of this study was to identify possible correlation between ULM and the ACE I/D polymorphism, to evaluate whether the ACE I/D polymorphism could be a marker for early diagnosis and prognosis. ACE I/D was amplified with specific primer sets recognizing genomic DNA from ULM (n=72) and control (n=83) volunteers and amplicons were separated on agarose gels. The observed genotype frequencies were in agreement with Hardy-Weinberg equilibrium ($x^2=2.162$, p=0.339). There was no association between allele frequencies and study groups ($x^2=0.623$; p=0.430 for ACE I allele, $x^2=0.995$; p=0.339 for ACE D allele). In addition, there were no significant differences between ACE I/D polymorphism genotype frequencies and ULM range in size and number ($X^2=1.760;$ p=0.415 for fibroid size, $X^2=0.342;$ p=0.843 for fibroid number). We conclude that the ACE gene I/D polymorphism is not related with the size or number of ULM fibroids in Turkish women. Thus it cannot be regarded as an early diagnostic parameter nor as a risk estimate for ULM predisposition.