Methylation and cancer: Review

WOS: 000257838900015DNA methylation is the major epigenetic modification in mammals, and is seen in CpG dinucleotides. In normal cells, the CpG dinucleotides in repetitive DNA are methylated, and CpG islands, which are found in the promotor region in 50% of genes, are demethylated. Epigenetic modifications may be defined as inheritable gene expression changes, without altering the primary sequence of DNA. It is well established that epigenetic modifications are as important as genetic changes in cancer development. Cancer cells show genomic hypomethylation and gene promotor hypermethylation. Both are independent from each other, but are effective in cancerogenesis in different ways. Hypermethylation of the promotor has a supressive effect on the downstream gene, and is important in turnout supressor gene inactivation. hMLH1 and O-6-MGMT gene methylations are the most studied among different cancer types. Knudson's two hit hypothesis is the most common hypotesis for cancer development, and one of these hits may be epigenetic. Genomewide hypomethylation may favor for genomic instability and reactivation of parasitic sequences. Promotor hypermethylation may show different patterns in different cancers, or different types of the same cancer, and methylation patterns may be useful as a cancer biomarker or a prognostic marker. Epigenetic mutations are reversible, and there is sparse promotor hypermethylation in normal cells, which makes demethylating agents highly specific for cancer cells. Increasing our knowledge on the methylation changes in cancer cells will improve our approaches to the treatment, diagnosis and prevention of cancer

CAG polymorphism in the androgen receptor gene in women may be associated with nodulocystic acne

Gunduz, Ozgur/0000-0003-1021-5219WOS: 000467799900007PubMed: 31320850Introduction: Acne vulgaris (AV) is a multifactorial, inflammatory disease of the pilosebaceous unit. Hormones play a major role in the pathogenesis of acne. In cases of hyperandrogenism; hirsutism, acne, seborrhoea and alopecia appear in women. However, severe acne can also be seen without evidence of hyperandrogenism. In this case, hypersensitivity of the androgen receptor gene (ARG) encoded in the X chromosome, which is the only receptor for androgens, can be considered. ARG contains a polymorphic CAG triple loop encoding the polyglutamine pathway at the 5'end of exon 1. Aim: To investigate CAG repeat polymorphism in the ARG in nodulocystic acne patients in Turkish population. Material and methods: This prospective clinical study was conducted between 2016 and 2017 in accordance with the tenets of the Declaration of Helsinki. DNA isolation from blood was performed using the RTA (R) Genomic DNA Isolation Kit. The fragment lengths obtained from the device to determine CAG repeat numbers were analysed based on -288 bp length 22 CAG repeat content. Results: A total of 199 subjects; 100 patients (51 males, 49 females) and 99 controls (49 males, 50 females) were included in the study. The mean allele length in the patient group was 19.34; and 19.7 in the control group. There was a statistically significant difference between female patients and the control group, when the patients and control groups were compared by gender (p = 0.0059). Conclusions: The CAG trinucleotide repeat count in the ARG may be associated with acne, without hirsutism findings.Kirikkale University Scientific Research Project Support Coordination UnitThis study was carried out with the support of the Kirikkale University Scientific Research Project Support Coordination Unit

The frequency of Familial Mediterranean fever gene mutations and genotypes at Kirikkale and comparison with the mean of regional MEFV mutation frequency of Turkey

WOS: 000332000400025PubMed: 24381109In this study we have retrospectively analysed the mutation spectrum of the 351 Familial Mediterranean fever patients referred to KA +/- rA +/- kkale University Faculty of Medicine, Department of Medical Genetics Laboratory over a period of 5 years and compared them with Turkey's mean. We have found 11 different mutations, including rare mutations such as F479L, K695R, M680I(G/A) and 45 different genotypes showing the heterogeneity of MEFV mutations in Central Anatolia. The most three prevalent mutations were M694V (14.8 %), E148Q (7.1 %) and M680I(G/C) (4.1 %) in accordance with the literature. We have also investigated R202Q in our routine molecular diagnosis. Mutation causing R202Q (c.605G > A) change was described as a frequent polymorphism and G allele was found in linkage disequilibrium (LD) with M694V. There are limited number of studies investigating R202Q, some of them implicate that its homozygote state is disease causing. We showed the high frequency of R202Q (23.7 %) with and without M694V in all the groups analysed and its high LD rate with M694V in the diagnosed group. Our study is reflecting the mutational heterogeneity of MEFV and summarize mutational spectrum of Turkey's geographical regions and overall Turkey

DNA methyltransferase expression differs with proliferation in childhood acute lymphoblastic leukemia

Ezer, Ustun/0000-0002-1536-7898; KARABULUT, HALIL GURHAN/0000-0002-2842-0029WOS: 000279308400044PubMed: 19763880…The Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK)We acknowledge to Timur Tuncali, Ongun Onaran and Uygar Tazebay for their technical support and to Kenan Kose for performing statistical analysis. This study was granted by The Scientific and Technological Research Council of Turkey (TUBITAK)

Interleukin (IL)-17F (H161R) and IL-23R (R381Q) Gene Polymorphisms in Turkish Population with Periodontitis

WOS: 000375075300002Background: Periodontitis is triggered by periodontal pathogens and influenced by environmental and genetic factors. Genes encoding molecules related to the immune response are the main candidates for polymorphisms analysis and may be possibly associated with this pathology. Aim: The aim of the study was to evaluate the interleukin (IL)-17F Histidine161Arginine (H161R) and IL-23R Arginine381Glycine (R381Q) gene polymorphisms in patients with periodontitis in Turkish population. Materials and Methods: 90 periodontally healthy, 90 patients with chronic periodontitis and 57 patients with generalized aggressive periodontitis were included in the study. Participants were identified through clinical examinations and radiographs. DNA was isolated from venous blood samples from each patient and genotype analyses were made for single nucleotide polymorphisms (SNPs). Data were analyzed using the x(2) test. Results: The comparison of allelic, genotypic frequencies of the IL-17F (H161R) and IL-23R (R381Q) polymorphisms revealed no significant differences between the periodontally healthy individuals and patients with periodontal diseases. Conclusion: On the basis of the present findings, it can be suggested that IL-17F gene (H161R) and IL-23R gene (R381Q) polymorphisms are not associated with the susceptibility to periodontitis in Turkish population

46, XX SRY(+) male sexual differentiation disorder with metabolic syndrome: A case report Metabolik sendromlu 46 XX SRY(+) erkek seksuel differansiyasyon bozukluǧu: Olgu sunumu

In disorders of sexual differentiation, sexual development may not be in accordance with chromosomal structure. 46,XX male syndrome is one of these kind of situations of which most of the patients are in normal male phenotype at birth. These patients are diagnosed while investigating for gynecomastia during puberty or infertility at older ages. One of the comorbidities of testosterone deficiency is metabolic syndrome. Recent studies have demonstrated a strong relationship between hypogonadism and metabolic syndrome. A 42-year-old male patient was admitted to our outpatient clinic with the complaint of gynecomastia. Based on laboratory tests results, he was diagnosed with hypergonadotropic hypogonadism accompanied by metabolic syndrome. Chromosomal analysis showed 46,XX SRY (+) genotype

The spectrum of FMF mutations and genotypes in the referrals to molecular genetic laboratory at K&Aumlaut +/- r&Aumlaut +/- kkale University in Turkey

WOS: 000263798400019PubMed: 18389382Familial Mediterranean Fever (FMF) is an autosomal recessive genetic disorder characterised by recurrent and self-limited abdominal pain, synovitis and pleuritis. MEFV gene mutations are responsible from the disease and its protein product, pyrin or marenostrin, plays an essential role in the regulation of the inflammatory reactions. MEFV gene contains 10 exons and most of the mutations have been found on the last exon. Up to date, 152 mutations and polymorpisms have been reported inwhere V726A, M694V, M694I, M680I and E148Q are the most common mutations. In this study, MEFV allele frequencies of 136 individuals (60 from Pediatry, 76 from Internal Medicine) have been evaluated, and compared with each other. Asymptomatic individuals with FMF family history (4 from Pediatry, 6 from Internal Medicine) were excluded from the analysis. The prominent mutations indicated in the Pediatry group are V726A, M694V and M680I (G/C) and with the allele frequency of 0.06, 0.05 and 0.04 respectively while they were E148Q, M694V, M680I (G/C) in the Internal Medicine group with the allele frequency of 0.12, 0.08 and 0.04. The E148Q mutation is significantly overrepresented in the adult referrals (P = 0.02). Mutation on both alleles was observed in only 12% of cases. Overall mutation frequency was low, seen in 26.2% (66/252). However, when only diagnosed patients were analyzed it is 72.7% (16/22). It is also interesting that 63% of individuals are female that there may be sex influence on FMF phenotype

The association of paraoxonase 1 gene L55M polymorphism with the extent and severity of coronary artery disease in the Turkish population and its dependence on gender

WOS: 000377193000007PubMed: 26467378Objective: Coronary artery disease (CAD) is a common, complex, and progressive disorder characterized by the accumulation of lipids and fibrous elements in the arteries. It is one of the leading causes of death in industrialized nations. Oxidative modification of low-density lipoprotein (LDL) in the arterial wall plays an important role in the initiation and progression of atherosclerosis. Paraoxonase1 (PON1) is involved in lipid metabolism and is believed to protect LDL oxidation. In our study, we aimed to clarify the relationship between PON1 gene L55M polymorphism and the extent and severity of CAD. Methods: In total, 114 patients (54 males, mean age: 56.7 +/- 12.0 years; 60 females, mean age: 55.7 +/- 13.2 years) with stable angina or angina equivalent symptoms were enrolled in this prospective study. Cardiological evaluation was performed with electrocardiogram and transthoracic echocardiogram. The presence of hypertension, dyslipidemia, diabetes, and smoking status were ascertained. The patients were grouped according to their Gensini scores and gender. Genetic analysis of the PON1 gene L55M polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism. Results: We determined that the LL genotype was more prevalent in patients with Gensini score higher than or equal to 20 (p=0.026) and that this correlated with severe atherosclerotic coronary artery lesions in both gender groups, reaching a statistical significance in the female subjects (p=0.038). Conclusion: It was thought that the PON1 gene L55M polymorphism plays a significant role in CAD progression, especially in females.Kirikkale University Scientific Research Projects Coordination UnitKirikkale University [2009/27]The study was supported through a grant (2009/27) by Kirikkale University Scientific Research Projects Coordination Unit