The association between the chromosome 9p21 CDKN2B-AS1 gene variants and the lipid metabolism: A pre-diagnostic biomarker for coronary artery disease

Objective: Recent genome-wide association studies have established that polymorphisms within CDKN2B-ASI of chr9p21.3 locus increased susceptibility to coronary artery disease (CAD) or myocardial infarction. Common variants of CDKN2B-AS1 (including rs4977574 A>G and rs1333040 C>T) are determined to be directly associated with CADs in many populations worldwide and suggested biomarkers for the early detection of CAD. There is a lack of investigation for the association between CDKN2B-AS1 rs4977574 A>G and rs1333040 C>T genetic modifiers and CAD in a Turkish Cypriot population. The aim of the present study was to investigate the potential effects of these variants on susceptibility to developing CAD in a Turkish Cypriot population and their contribution to lipid metabolism. Methods: Seventy-one patients with angiography-confirmed CAD were recruited to the CAD group, whereas 153 voluntary subjects without CAD symptoms were enrolled to the control group. Genotyping for the CDKN2B-AS1 gene polymorphisms was performed by polymerase chain reaction, followed by restriction fragment length polymorphism analysis. Results: There is no statistical significant association observed between rs4977574 and rs1333040 single-nucleotide polymorphisms and two studied groups [odds ratio (OR): 0.763, p=0.185, 95% confidence interval (CI): 0.511-1.139 and OR: 1.060, p=0.802, 95% CI: 0.672-1.671, respectively]. However, rs2977574 G and rs1333040 T alleles-the risk alleles-were found to be associated with higher level of serum total cholesterol and lower level of high-density lipoprotein-cholesterol in the CAD group (p=0.019, p=0.006 and p=0.022, p=0.031, respectively). To our knowledge, this is the first study that establishes the effect of rs1333040 on lipid metabolism. Conclusion: The presence of rs4977574 G and rs1333040 T alleles and interaction may exist as environmental factors associated with lipid metabolism and might be responsible for the development of CAD in a Turkish Cypriot population

Letter to the editor regarding the article “A case of hypertrophic and dilated cardiomyopathic sudden cardiac death: de novo mutation in TTN and SGCD genes”

We recently read the article entitled “A case of hypertrophic and dilated cardiomyopathic sudden cardiac death: de novo mutation in TTN and SGCD genes” by Baydar et al. (1) published in the Anatolia Journal of Cardiology in late 2016 with great interest. We commend the authors for their contribution to improving our understanding of sudden cardiac death mechanisms and suggesting potential reasons for occurrence of the condition of genetic origin. We do, however, have a number of thoughts about the study, which are outlined below. The authors mentioned de novo mutation in the sarcoglycan (SGCD) and titin (TTN) genes. The article fails to mention, however, the parent-based variant approach to analysis. In human genetic diseases, the term “de novo mutation” by definition refers to an alteration in a gene that is present for the first time in one family member as a result of a mutation in a germ cell of one of the parents or in the zygote itself. It is only by analyzing the parents that their true contribution to the disease burden can be proven

Strong association between VDR FokI (rs2228570) gene variant and serum vitamin D levels in Turkish Cypriots

Vitamin D is an important molecule to keep teeth, bones and muscles healthy. It is obtained from diet, supplements and primarily from exposure to sunlight. In recent years, vitamin D deficiency is recognised as a worldwide health problem, which results in disturbances in mineral metabolism and skeletal problems. Deficiency might be caused due to sedentary lifestyle, insufficient diet, age as well as some polymorphisms in the VDR gene. In this study the four most common VDR polymorphisms (rs1544410 (BsmI), rs731236 (TaqI), rs7975232 (ApaI) and rs2228570 (FokI)) are investigated in a cohort of Turkish Cypriots and aimed to detect any possible links between low serum vitamin D levels and these variants. The rs2228570 (FokI) variant but not others were shown to have a significant association with decreased serum vitamin D levels in the Turkish Cypriot population

Functional coding/non-coding variants in EGFR, ROS1 and ALK genes and their role in liquid biopsy as a personalized therapy

Personalized medicine holds promise to tailor the treatment options for patients' unique genetic make-up, behavioral and environmental background. Liquid biopsy is non-invasive technique and precise diagnosis and treatment approach. Significantly, NGS technologies have revolutionized the genomic medicine by novel identifying SNPs, indel mutations in both coding and non-coding regions and also a promising technology to accelerate the early detection and finding new biomarkers for diagnosis and treatment. The number of the bioinformatics tools have been rapidly increasing with the aim of learning more about the detected mutations either they have a pathogenic role or not. EGFR, ROS1 and ALK genes are members of the RTK family. Until now, mutations within these genes have been associated with many cancers and involved in resistance formation to TKIs. This review article summarized the findings about the mostly investigated variations in EGFR, ROS1 and ALK genes and their potential role in liquid biopsy approach

A Multicenter Study of Genotype Variation/Demographic Patterns in 2475 Individuals Including 1444 Cases With Breast Cancer in Turkey

Objective: Breast cancer (BC) is the most common cancer type in women and may be inherited, mostly in an autosomal dominant pattern. The clinical diagnosis of BC relies on the published diagnostic criteria, and analysis of two genes, BRCA1 and BRCA2, which are strongly associated with BC, are included in these criteria. The aim of this study was to compare BC index cases with non-BC individuals in terms of genotype and diagnostic features to investigate the genotype/demographic information association. Materials and Methods: Mutational analyses for the BRCA1/BRCA2 genes was performed in 2475 individuals between 2013-2022 from collaborative centers across Turkey, of whom 1444 with BC were designated as index cases. Results: Overall, mutations were identified in 17% (421/2475), while the percentage of mutation carriers in cases of BC was similar, 16.6% (239/1444). BRCA1/BRCA2 gene mutations were detected in 17.8% (131/737) of familial cases and 12% (78/549) of sporadic cases. Mutations in BRCA1 were found in 4.9%, whereas 12% were in BRCA2 (p<0.05). Meta-analyses were performed to compare these results with other studies of Mediterranean-region populations. Conclusion: Patients with BRCA2 mutations were significantly more common than those with BRCA1 mutations. In sporadic cases, there was a lower proportion with BRCA1/BRCA2 variants, as expected, and these results were consistent with the data of Mediterranean-region populations. However, the present study, because of the large sample size, revealed more robust findings than previous studies. These findings may be helpful in facilitating the clinical management of BC for both familial and non-familial cases