Critical appraisal of the private genetic and pharmacogenomic testing environment in Greece

Aim: In the postgenomic era, we are witnessing rapid progress in the identification of the molecular basis of human inherited disorders and the elucidation of genotype–phenotype relationships. The rate of progress has been driven not only by the determination and ongoing decipherment of the human genome sequence but also by the advent of new technological developments that have dramatically reduced the costs of genetic analysis. As a consequence, a considerable number of genetic testing centers have emerged, both in Europe and the USA, which together offer a plethora of different genetic tests. Methods: We have performed a nationwide survey of 18 private genetic testing laboratories in Greece in order to acquire a better understanding of the genetic testing services that these centers provide, specifically the types of genetic test offered, the target groups, marketing channels, costs of analysis and accreditation. Results: Molecular genetic and cytogenetic testing were found to be the predominant types of genetic testing services offered although there is an increasing demand for pharmacogenomic testing. The main target group for private genetic testing laboratories is the physicians who are approached via the internet, through personal contacts from sales representatives and at scientific conferences. Genetic testing costs are fairly low in Greece. Although the majority of private genetic laboratories either employ or collaborate with a genetic counselor, few of them are accredited for the provision of genetic testing services. Conclusion: This study constitutes the basis for a critical appraisal of the private genetic testing environment in Greece and provides a model for replication in other European countries

Wireless Direct Microampere Current in Wound Healing: Clinical and Immunohistological Data from Two Single Case Reports

Chronic pressure ulcers are hard-to-heal wounds that decrease the patient’s quality of life. Wireless Micro Current Stimulation (WMCS) is an innovative, non-invasive, similar to electrode-based electrostimulation (ES) technology, that generates and transfers ions that are negatively-charged to the injured tissue, using accessible air gases as a transfer medium. WMCS is capable of generating similar tissue potentials, as electrode-based ES, for injured tissue. Here, through immunohistochemistry, we intended to characterize the induced tissue healing biological mechanisms that occur during WMCS therapy. Two single cases of bedridden due to serious stroke white men with chronic non-healing pressure ulcers have been treated with WMCS technology. WMCS suppresses inflammatory responses by decreasing the aggregation of granulocytes, followed by stimulating myofibroblastic activity and a new formation of collagen fibers, as depicted by immunohistochemistry. As a result, WMCS provides a special adjunct or stand-alone therapy choice for chronic and non-healing injuries, similar to electrode-based ES, but with added (i.e., contactless) benefits towards its establishment as a routine clinical wound healing regime

Ascertainment and critical assessment of the views of the general public and healthcare professionals on nutrigenomics in Greece

Aim: The aim of this study was to understand the general public’s and healthcare professionals’ views on nutrigenomics. Patients & methods: We designed a cross-sectional survey of healthcare professionals (n = 87) and the general public (n = 1504) in the three largest cities in Greece (Athens, Thessaloniki and Patras). Results: Our data revealed that only 11.5% of respondents from the general public had been advised to take a genetic test in order to explore the relationship between their genes and their nutritional status. Although 80.5% of healthcare professionals would have been willing to recommend their patients/clients to undergo nutrigenomic analysis to correlate their genetic profile with their diet, only 17.2% of respondents had actually done so. In general, the general public was opposed to direct-access nutrigenomics testing. Conclusion: The application of genomic information in the context of nutritional choice requires the continuing education of healthcare professionals and the dissemination of accurate and reliable information to the general public

ETHNOS: A versatile electronic tool for the development and curation of national genetic databases

National and ethnic mutation databases (NEMDBs) are emerging online repositories, recording extensive information about the described genetic heterogeneity of an ethnic group or population. These resources facilitate the provision of genetic services and provide a comprehensive list of genomic variations among different populations. As such, they enhance awareness of the various genetic disorders. Here, we describe the features of the ETHNOS software, a simple but versatile tool based on a flat-file database that is specifically designed for the development and curation of NEMDBs. ETHNOS is a freely available softw

ETHNOS : A versatile electronic tool for the development and curation of national genetic databases.

National and ethnic mutation databases (NEMDBs) are emerging online repositories, recording extensive information about the described genetic heterogeneity of an ethnic group or population. These resources facilitate the provision of genetic services and provide a comprehensive list of genomic variations among different populations. As such, they enhance awareness of the various genetic disorders. Here, we describe the features of the ETHNOS software, a simple but versatile tool based on a flat-file database that is specifically designed for the development and curation of NEMDBs. ETHNOS is a freely available software which runs more than half of the NEMDBs currently available. Given the emerging need for NEMDB in genetic testing services and the fact that ETHNOS is the only off-the-shelf software available for NEMDB development and curation, its adoption in subsequent NEMDB development would contribute towards data content uniformity, unlike the diverse contents and quality of the available gene (locus)-specific databases. Finally, we allude to the potential applications of NEMDBs, not only as worldwide central allele frequency repositories, but also, and most importantly, as data warehouses of individual-level genomic data, hence allowing for a comprehensive ethnicity-specific documentation of genomic variation

A critical view of the general public's awareness and physicians' opinion of the trends and potential pitfalls of genetic testing in Greece

Aim: Progress in deciphering the functionality of the human genome sequence in the wake of technological advances in the field of genomic medicine have dramatically reduced the overall costs of genetic analysis, thereby facilitating the incorporation of genetic testing services into mainstream clinical practice. Although Greek genetic testing laboratories offer a variety of different genetic tests, relatively little is known about how either the general public or medical practitioners perceive genetic testing services. Materials & methods: We have therefore performed a nationwide survey of the views of 1717 members of the general public, divided into three age groups, from all over Greece, and residing in both large and small cities and villages, in order to acquire a better understanding of how they perceive genetic testing. We also canvassed the opinions of 496 medical practitioners with regard to genetic testing services in a separate survey that addressed similar issues. Results: Our subsequent analysis indicated that a large proportion of the general public is aware of the nature of DNA, genetic disorders and the potential benefits of genetic testing, although this proportion declines steadily with age. Furthermore, a large proportion of the interviewed individuals would be willing to undergo genetic testing even if the cost of analysis was not covered by healthcare insurance. However, a relatively small proportion of the general public has actually been advized to undergo genetic testing, either by relatives or physicians. Most physicians believe that the regulatory and legal framework that governs genetic testing services in Greece is rather weak. Interestingly, the vast majority of the general public strongly opposes direct-access genetic testing, and most would prefer referral from a physician than from a pharmacist. Conclusion: Overall, our results provide a critical evaluation of the views of the general public with regard to genetics and genetic testing services in Greece and should serve as a model for replication in other populations

FINDbase: a worldwide database for genetic variation allele frequencies updated

Frequency of INherited Disorders database (FIND base; http://www.findbase.org) records frequencies of causative genetic variations worldwide. Database records include the population and ethnic group or geographical region, the disorder name and the related gene, accompanied by links to any related external resources and the genetic variation together with its frequency in that population. In addition to the regular data content updates, we report the following significant advances: (i) the systematic collection and thorough documentation of population/ethnic group-specific pharmacogenomic markers allele frequencies for 144 markers in 14 genes of pharmacogenomic interest from different classes of drug-metabolizing enzymes and transporters, representing 150 populations and ethnic groups worldwide; (ii) the development of new data querying and visualization tools in the expanded FINDbase data collection, built around Microsoft’s PivotViewer software (http://www.getpivot.com), based on Microsoft Silverlight technology (http://www.silverlight.net) that facilitates querying of large data sets and visualizing the results; and (iii) the establishment of the first database journal, by affiliating FINDbase with Human Genomics and Proteomics, a new open-access scientific journal, which would serve as a prime example of a non-profit model for sustainable database funding

Novel genetic risk variants for pediatric celiac disease

Background: Celiac disease is a complex chronic immune-mediated disorder of the small intestine. Today, the pathobiology of the disease is unclear, perplexing differential diagnosis, patient stratification, and decision-making in the clinic. Methods: Herein, we adopted a next-generation sequencing approach in a celiac disease trio of Greek descent to identify all genomic variants with the potential of celiac disease predisposition. Results: Analysis revealed six genomic variants of prime interest: SLC9A4 c.1919G gt A, KIAA1109 c.2933T gt C and c. 4268_4269delCCinsTA, HoxB6 c.668C gt A, HoxD12 c.418G gt A, and NCK2 c.745_746delAAinsG, from which NCK2 c.745_746delAAinsG is novel. Data validation in pediatric celiac disease patients of Greek (n=109) and Serbian (n=73) descent and their healthy counterparts (n=111 and n=32, respectively) indicated that HoxD12 c.418G gt A is more prevalent in celiac disease patients in the Serbian population (P lt 0.01), while NCK2 c.745_746delAAinsG is less prevalent in celiac disease patients rather than healthy individuals of Greek descent (P = 0. 03). SLC9A4 c.1919G gt A and KIAA1109 c.2933T gt C and c.4268_4269delCCinsTA were more abundant in patients; nevertheless, they failed to show statistical significance. Conclusions: The next-generation sequencing-based family genomics approach described herein may serve as a paradigm towards the identification of novel functional variants with the aim of understanding complex disease pathobiology

VAV1 and BAFF, via NFκB pathway, are genetic risk factors for myasthenia gravis

Objective To identify novel genetic loci that predispose to early‐onset myasthenia gravis (EOMG) applying a two‐stage association study, exploration, and replication strategy. Methods Thirty‐four loci and one confirmation loci, human leukocyte antigen (HLA)‐DRA, were selected as candidate genes by team members of groups involved in different research aspects of MG. In the exploration step, these candidate genes were genotyped in 384 EOMG and 384 matched controls and significant difference in allele frequency were found in eight genes. In the replication step, eight candidate genes and one confirmation loci were genotyped in 1177 EOMG patients and 814 controls, from nine European centres. Results Allele frequency differences were found in four novel loci: CD86, AKAP12, VAV1, B‐cell activating factor (BAFF), and tumor necrosis factor‐alpha (TNF‐α), and these differences were consistent in all nine cohorts. Haplotype trend test supported the differences in allele frequencies between cases and controls. In addition, allele frequency difference in female versus male patients at HLA‐DRA and TNF‐α loci were observed. Interpretation The genetic associations to EOMG outside the HLA complex are novel and of interest as VAV1 is a key signal transducer essential for T‐ and B‐cell activation, and BAFF is a cytokine that plays important roles in the proliferation and differentiation of B‐cells. Moreover, we noted striking epistasis between the predisposing VAV1 and BAFF haplotypes; they conferred a greater risk in combination than alone. These, and CD86, share the same signaling pathway, namely nuclear factor‐kappaB (NFκB), thus implicating dysregulation of proinflammatory signaling in predisposition to EOMG

Are Metals Emitted from Electronic Cigarettes a Reason for Health Concern? A Risk-Assessment Analysis of Currently Available Literature

Background: Studies have found that metals are emitted to the electronic cigarette (EC) aerosol. However, the potential health impact of exposure to such metals has not been adequately defined. The purpose of this study was to perform a risk assessment analysis, evaluating the exposure of electronic cigarette (EC) users to metal emissions based on findings from the published literature. Methods: Two studies were found in the literature, measuring metals emitted to the aerosol from 13 EC products. We estimated that users take on average 600 EC puffs per day, but we evaluated the daily exposure from 1200 puffs. Estimates of exposure were compared with the chronic Permissible Daily Exposure (PDE) from inhalational medications defined by the U.S. Pharmacopeia (cadmium, chromium, copper, lead and nickel), the Minimal Risk Level (MRL) defined by the Agency for Toxic Substances and Disease Registry (manganese) and the Recommended Exposure Limit (REL) defined by the National Institute of Occupational Safety and Health (aluminum, barium, iron, tin, titanium, zinc and zirconium). Results: The average daily exposure from 13 EC products was 2.6 to 387 times lower than the safety cut-off point of PDEs, 325 times lower than the safety limit of MRL and 665 to 77,514 times lower than the safety cut-off point of RELs. Only one of the 13 products was found to result in exposure 10% higher than PDE for one metal (cadmium) at the extreme daily use of 1200 puffs. Significant differences in emissions between products were observed. Conclusions: Based on currently available data, overall exposure to metals from EC use is not expected to be of significant health concern for smokers switching to EC use, but is an unnecessary source of exposure for never-smokers. Metal analysis should be expanded to more products and exposure can be further reduced through improvements in product quality and appropriate choice of materials