Current Pharmacogenomics and Personalized Medicine (Formerly Current Pharmacogenomics) - Volume 13, Issue 1, 2015

Background: Although clinicians failed to reproduce Pauling and Cameron’s earlier reports on the therapeutic effects of vitamin C on cancer, new information on the pharmacokinetics and pharmacodynamics of vitamin C as well as new clinical data has provided more in depth understanding of the critical aspects of vitamin C’s therapeutic effects. Previous clinical studies suggested that vitamin C, introduced to cancer patients by intravenous and oral pathways, might improve their symptoms. Methods: This review summarizes and focuses on different pharmacological effects of vitamin C that are currently under investigation in pharmacogenomic studies related to transporter gene polymorphism. Conclusion: From the information available, it seems clear that vitamin C is involved in a variety of disease mechanisms. This review might provide an evaluation of vitamin C as a personalized adjuvant medicine.

Background: Individual drug response arises from the interplay between genes and the environment. Pharmacometabolomics, is an alternative, but complementary discipline to pharmacogenomics, aiming to predict or evaluate response to treatment. Methods: Data for this perspective article were identified by searches of PubMed and references from relevant articles using the search terms "pharmacogenomics", "pharmacometabolomics", and "personalized medicine". Only articles published in English between 2002 and 2015 were included. Results: This perspective article on pharmacometabolomics focuses on the current applications of this holistic approach and presents the challenges that still need to be met. Conclusion: The merge of pharmacogenomics with pharmacometabolomic data, rapidly and efficiently, remains a significant challenge. No doubt, a “pharmacometabolomics-informed pharmacogenomic” strategy is anticipated to enable our in-depth understanding of individual variations in drug response phenotypes and hence, the design of individualized therapeutic approaches via the prediction of metabotypes.

Background: Nutraceuticals are bioactive substances which are known for their therapeutic activity against a wide range of diseases. The term nutraceutical is derived from the terms ‘nutrition’ and ‘pharmaceuticals’ and refers to a food product that elicits medical health benefits for the prevention and cure of diseases. A nutraceutical has been investigated and indicated to exhibit physiological benefits and protection against various chronic diseases like cancers, cardiovascular disorders, Alzheimer’s disease, diabetes, etc. Aim: The aim of the current review article is to distinguish nutraceuticals from possibly confusing terms like functional foods, medical foods, and dietary supplements with their detailed classification. This paper presents the use of researched nutraceutical products to treat various diseases. Last, the attention on the commercialized nutraceutical products with certain safety regulations is elaborated as a growing concern. Nutraceuticals will be greatly important in human health as they provide all the essential components of a healthy diet. Conclusion & Future: With an aim to improve the quality of life at present, nutraceutical represents the fastest-growing segment of today’s food industry. The future is centered on the newly designed foods stocked at the supermarkets providing a better standard of life, giving a healthier way of living to people reaching throughout the world.

Background: Tuberculosis (TB) is one of the most important causes of mortality due to infectious diseases. The development of a vaccine inducing superior protection than BCG is a top priority for the future control of the disease. Methods: We reviewed the literature related with the impact of the host, microbiome and environmental elements in response to vaccination, with special emphasis on TB. Results: This review introduces the term “Self-Antigenic Universe” (SAU) which consists of “Host” & “Guests” (classical microbiota and other organisms with relatively stable presence in the host) and “Familiar Visitors”: (organisms and substances which are often present in the host). We provide multiple examples of how SAU influences the immune response to Mycobacterium tuberculosis and its impact on TB vaccine development. Conclusion: The immune response induced by antigens/epitopes present in SAU could have carrier effect and elicit specific effector and/or regulatory immune responses potentially useful for the development of new vaccines. This aspect should be considered for the development of tailored vaccines with superior efficacy for the prevention of TB.

Background: It is well-documented that though living in the same geographical area, European Roma and their host populations have distinct genetic ancestries. Nevertheless, there are very few studies addressing diversity of pharmacogenetic significance in Roma groups. The main goal of the present study was to characterise the Portuguese Gypsies for a selected battery of SNPs located in genes known to influence the response to drugs (TPMT, CYP2C9, CYP2C19, NAT2, and VKORC1) in comparison to their host population. Methods: The DNA of 116 Portuguese Gypsies and 70 Portuguese non-Gypsies individuals was genotyped using a multiplex PCR-minisequencing assay for the following SNPs: TPMT*2, TPMT*3B, TPMT*3C, TPMT*8, CYP2C9*2, CYP2C9*3, CYP2C19*2, NAT2*5, NAT2*13, and VKORC1 c.-1639G>A. Comparative analyses were performed and extended to other populations for which allelic frequencies were available from the literature. Results: Comparisons between Portuguese Gypsies and non-Gypsies only revealed significant differences for CYP2C9*2. In the worldwide geographical context, both samples fitted well the pattern of pharmacogenetic diversity found in Europe. However, in the Euro-Indian framework, Gypsies revealed to be closer to Indian populations, especially from North India, than did the Portuguese non-Gypsies. Conclusion: From the pharmacogenetic point of view, the Gypsies from Portugal do not seem to raise additional public health concerns comparatively to other Portuguese. This study illustrates how important signs of the demographic past of a population can be captured by the fraction of pharmacogenetically relevant genetic diversity.

Background: Particulate pollution is associated with occurrence of asthma and allergy, acting together with allergens in initiating and exacerbating these diseases. Production of reactive oxygen species contributes to this effect of pollutants. We tested the hypothesis that oxygen radicals generated by granulocytes are key regulators in exacerbation of allergic responses by particulate pollution. Methods: Out of pollen season, granulocytes and serum were collected from 17 patients sensitive to pollen allergens and from 13 healthy volunteers. Oxygen radical generation, individual single nucleotide polymorphism types (SOD2, SOD3, GSTP1, CAT, FCER1B and IL4A) , gene expression differences and serum cytokine concentrations were compared with allergen-specific IgE, and histamine-release test results in ability to discriminate between groups. Results: Oxygen radical measurements predicted severity of pollinosis. Allergy (IgE receptor) related genotype FCER1B was associated with increased oxygen radical generation (P=0.04). RNA markers may also predict the onset of hay fever those symptoms getting worse. Interpretation. From our pilot study, genomic approaches and oxygen radical generation by granulocytes in response to pollen particles may be possible molecular markers of allergic inflammation that predicted pollinosis severity. Conclusion: New measurement technique and methodology may elucidate pollinosis patients in their prediction and prevention and may contribute to development of preventive medicine. It is only a pilot study with small sample, but might have possibilities of finding a cut end and a breakthrough in the difficulty of allergic pathophysiology from the viewpoint of genomic approach and radical oxygen measurement.

Background: Conventional organic fluorescent labels are currently being employed for detection of query molecules on protein microarrays platform; however, they exhibit certain limitations like poor photo-stability, overlapped emission/excitation spectra, autofluorescence, limited sensitivity, rigorous sample preparation procedures and are expensive. Objective: Objective of this study was to develop new labels which can overcome the limitations associated with existing labels and can be used with existing microarrays setup. Nanophosphor labels seem to be the most promising nano-material, which could overcome most of these limitations. Yttrium oxide (Y2O3) doped with 1.5% Gadolinium (Gd) and 2% Europium (Eu) has a quantum efficiency of about 70%. The emission wavelength lies in red region (612 nm) and could be excited in green region (532 nm), therefore it could be employed with existing microarrays instrumentation setup. Method: Y2O3: Eu, Gd nanophosphor labels were synthesized by Pechini-type in situ polymerizable complex (IPC) method. Surface modification was done by modified Strober method, for their bioconjugation with proteins/antibodies via amine-carboxylic zero-length cross-linking mechanism. Results: Bovine Serum Albumin (BSA) and anti-BSA were bioconjugated with Y2O3: Eu, Gd nanophosphor labels and their application on reverse phase protein/antibody microarrays platform was demonstrated as a proof of concept. Specificity and limit of detection of Y2O3: Gd, Eu labels was determined on protein/antibody microarray platform using nanophosphors labeled Glutathione S-transferases (GST) and anti-GST. Conclusion: These novel nanophosphors-based labels have potential to overcome several limitations of existing labels and hence could be employed for the protein microarrays applications.

Background: The response to thiopurine treatment in inflammatory bowel disease patients differs greatly among individuals and nearly 50% of patients experience no benefit. Several factors have been implicated in determining this response, including individual genetic variation. Methods: Aiming to identify genes involved in the response to thiopurine drugs, a two-stage investigation of 20,000 coding single-nucleotide polymorphisms (cSNPs) in 10,000 genes was performed in a Spanish cohort of 257 individuals, 193 showing steroid free remission versus 64 non responder individuals 12 months after initial dose of the drug. The 20 top cSNPs with lower p-values for the association test identified at the first stage (133 responders / 34 non responders), were replicated in a second cohort (60 responders / 30 non responders). Results: Whereas not statistically significant in all of the two analyzed cohorts, the consistent across samples direction of the observed associations and the allelic joined analysis suggest a significant risk for lack of response related to two genes, PION and ZNF673. With a CMH p-value= 4.26x-06, the associated PION cSNP (rs17151692) minor A allele increases risk for treatment failure 4.5 times when all data is combined. Conclusion: These findings might help to understand the biological mechanisms behind thiopurine treatment failure and to tailor treatment for individual inflammatory bowel disease patients.