The influence of carboxylesterase 1 polymorphism and cannabidiol on the hepatic metabolism of heroin.

Chem Biol Interact. 2019 Dec 11;:108914

Authors: Qian Y, Gilliland TK, Markowitz JS

Abstract
Heroin (diamorphine) is a highly addictive opioid drug synthesized from morphine. The use of heroin and incidence of heroin associated overdose death has increased sharply in the US. Heroin is primarily metabolized via deacetylation (hydrolysis) forming the active metabolites 6-monoacetylmorphine (6-MAM) and morphine. A diminution in heroin hydrolysis is likely to cause higher drug effects and toxicities. In this study, we sought to determine the contribution of the major hepatic hydrolase carboxylesterase 1 (CES1) to heroin metabolism in the liver as well as the potential influence of one of its known genetic variants, G143E (rs71647871). Furthermore, given the potential therapeutic application of cannabidiol (CBD) for heroin addiction and the frequent co-abuse of cannabis and heroin, we also assessed the effects of CBD on heroin metabolism. In vitro systems containing human liver, wild-type CES1, and G143E CES1 S9 fractions were utilized in the assessment. The contribution of CES1 to the hydrolysis of heroin to 6-MAM was determined as 3.66%, and CES1 was unable to further catalyze 6-MAM under our assay conditions. The G143E variant showed a 3.2-fold lower intrinsic clearance of heroin as compared to the WT. CBD inhibited heroin and 6-MAM hydrolysis in a reversible manner, with IC50s of 14.7 and 12.1 μM, respectively. Our study results suggested only minor involvement of CES1 in heroin hydrolysis in the liver. Therefore, the G143E variant is unlikely to cause significant impact despite a much lower hydrolytic activity. CBD exhibited potent in vitro inhibition toward both heroin and 6-MAM hydrolysis, which may be of potential clinical relevance.

PMID: 31837295 [PubMed - as supplied by publisher]

Hepatic Estrogen Sulfotransferase Distantly Sensitizes Mice to Hemorrhagic Shock-Induced Acute Lung Injury.

Endocrinology. 2019 Dec 14;:

Authors: Xie Y, Barbosa ACS, Xu M, Oberly PJ, Ren S, Gibbs RB, Poloyac SM, Song W, Fan J, Xie W

Abstract
Hemorrhagic shock (HS) is a potential life-threatening condition that may lead to injury to multiple organs, including the lung. The estrogen sulfotransferase (EST, or SULT1E1) is a conjugating enzyme that sulfonates and deactivates estrogens. In this report, we showed that the expression of Est was markedly induced in the liver, but not in the lung of female mice subject to hemorrhagic shock and resuscitation (HS/R). Genetic ablation or pharmacological inhibition of Est effectively protected female mice from HS-induced acute lung injury (ALI), including interstitial edema, neutrophil mobilization and infiltration, and inflammation. The pulmonoprotective effect Est ablation or inhibition was sex-specific, because the HS-induced ALI was not affected in male Est-/- mice. Mechanistically, the pulmonoprotective phenotype in female Est-/- mice was accompanied by increased lung and circulating levels of estrogens, attenuated pulmonary inflammation, and inhibition of neutrophil mobilization from the bone marrow and infiltration to the lung, whereas the pulmonoprotective effect was abolished upon ovariectomy, suggesting that the pulmonoprotective effect was estrogen dependent. The pulmonoprotective effect of Est ablation was also tissue-specific, as loss of Est had little effect on HS-induced liver injury. Moreover, transgenic reconstitution of human EST in the liver of global Est-/- mice abolished the pulmonoprotective effect, suggesting that it is the EST in the liver that sensitizes mice to HS-induced ALI. Taken together, our results revealed a sex- and tissue-specific role of EST in HS-induced ALI. Pharmacological inhibition of EST may represent an effective approach to manage HS-induced ALI.

PMID: 31837219 [PubMed - as supplied by publisher]

Vitamin D Supplementation Ameliorates Severity of Major Depressive Disorder.

J Mol Neurosci. 2019 Dec 13;:

Authors: Alghamdi S, Alsulami N, Khoja S, Alsufiani H, Tayeb HO, Tarazi FI

Abstract
Major depressive disorder is a serious neuropsychiatric disease that leads to significant impairment in social functioning and increased morbidity and mortality. Low vitamin D (25-OH D) levels have been hypothesized to contribute to the pathophysiology of MDD. To investigate the therapeutic role of vitamin D in MDD, we recruited 62 male and female patients diagnosed with MDD and randomized them into two groups: the first group (49 patients) received vitamin D supplementation as cholecalciferol vitamin D3 (50,000 I.U.) for 3 months, in addition to standard of care (SOC) which included pharmacological treatment and psychological support, and the second group (13 patients) received only SOC without vitamin D supplementation for 3 months. The Beck depression inventory (BDI) scale was used to assess the severity of MDD symptoms. Immunoassays were utilized to determine levels of serum vitamin D3 and serotonin in all patients. The results showed significant gender differences; female patients showed the most improvement in their depressive symptoms after 3-month vitamin D supplementation. Females with moderate, severe, and extreme depression had significantly lower BDI scores after vitamin D treatment (p < 0.05). Among males, only those diagnosed with severe depression showed significant improvement in their BDI scores (p < 0.05). Serum serotonin levels were significantly increased after vitamin D supplementation compared to baseline in both male and female patients. No significant changes in other biochemical parameters were detected between the two groups. These findings suggest that vitamin D supplementation may ameliorate symptoms of MDD, particularly in females, via a serotonin-dependent mechanism.

PMID: 31836995 [PubMed - as supplied by publisher]

Economic Burden of Depression and Associated Resource Use in Manitoba, Canada.

Can J Psychiatry. 2019 Dec 13;:706743719895342

Authors: Tanner JA, Hensel J, Davies PE, Brown LC, Dechairo BM, Mulsant BH

Abstract
OBJECTIVES: To characterize the health-care utilization and economic burden associated with depression in Manitoba, Canada.
METHODS: Patient-level data were retrieved from the Manitoba Centre for Health Policy administrative, clinical, and laboratory databases for the study period of January 1, 1996, through December 31, 2016. Patients were assigned to the depression cohort based on diagnoses recorded in hospitalizations and outpatient physician claims, as well as antidepressant prescription drug claims. A comparison cohort of nondepressed subjects, matched with replacement for age, gender, place of residence (urban vs. rural), and index date, was created. Demographics, comorbidities, intentional self-harm, mortality, health-care utilization, prescription drug utilization, and costs of health-care utilization and social services were compared between depressed patients and matched nondepressed patients, and incidence rate ratios and hazard ratios were reported.
RESULTS: There were 190,065 patients in the depression cohort and 378,177 patients in the nondepression cohort. Comorbidities were 43% more prevalent among depressed patients. Intentional self-harm, all-cause mortality, and suicide mortality were higher among patients with depression than the nondepression cohort. Health-care utilization-including hospitalizations, physician visits, physician-provided psychotherapy, and prescription drugs-was higher in the depression than the nondepression cohort. Mean health-care utilization costs were 3.5 times higher among depressed patients than nondepressed patients ($10,064 and $2,832, respectively). Similarly, mean social services costs were 3 times higher ($1,522 and $510, respectively). Overall, depression adds a total average cost of $8,244 (SD = $40,542) per person per year.
CONCLUSIONS: Depression contributes significantly to health burden and per patient costs in Manitoba, Canada. Extrapolation of the results to the entire Canadian health-care system projects an excess of $12 billion annually in health system spending.

PMID: 31835904 [PubMed - as supplied by publisher]

Mechanisms of resistance and predictive biomarkers of response to targeted therapies and immunotherapies in metastatic melanoma.

Curr Opin Oncol. 2019 Dec 10;:

Authors: Mourah S, Louveau B, Dumaz N

Abstract
PURPOSE OF REVIEW: Thanks to mitogen-activated protein kinase inhibitors (MAPKi) and immune checkpoint inhibitors (ICI), major progress has been made in the field of melanoma treatment. However, long-term success is still scarce because of the development of resistance. Understanding these mechanisms of resistance and identifying predictive genomic biomarkers are now key points in the therapeutic management of melanoma patients.
RECENT FINDINGS: Multiple and complex mechanisms of resistance to MAPKi or ICI have been uncovered in the past few years. The lack of response can be driven by mutations and nonmutational events in tumor cells, as well as by changes in the tumor microenvironment. Melanoma cells are also capable of rapidly switching their molecular and cellular phenotype, leading to an initial drug-tolerant favorizing melanoma resistance. Tumor molecular profiling and circulating tumor cell analyses are of high interest as predictive biomarkers as well as studying immunogenic changes and microbiome in ICI-treated patients.
SUMMARY: Resistance to MAPKi and ICI is a key point in therapeutic management of metastatic melanoma patients. Validated biomarkers predicting response to therapy are urgently needed to move toward personalized medicine. Combinatory treatments guided by the understanding of resistance mechanisms will be of major importance in the future of melanoma therapy.

PMID: 31833956 [PubMed - as supplied by publisher]

Basic Concepts in Genetics and Pharmacogenomics for Pharmacists.

Drug Target Insights. 2019;13:1177392819886875

Authors: Orrico KB

Abstract
This basic review of genetic principles will aid pharmacists in preparing for their eventual role of translating gene-drug associations into clinical practice. Genes, which are stretches of deoxyribonucleic acid (DNA) contained on the 23 pairs of human chromosomes, determine the size and shape of every protein a living organism builds. Variation in pharmacogenes which encode for proteins central to drug action and toxicity serves as the basis of pharmacogenomics (PGx). Important online resources such as PharmGKB.org, cpicpgx.org, and PharmVar.org provide the clinician with curated and summarized PGx associations and clinical guidelines. As genetic testing becomes increasingly affordable and accessible, the time is now for pharmacists to embrace PGx-guided medication selection and dosing to personalize and improve the safety and efficacy of drug therapy.

PMID: 31832012 [PubMed]

Unveiling the guidance heterogeneity for genome-informed drug treatment interventions among regulatory bodies and research consortia.

Pharmacol Res. 2019 Dec 09;:104590

Authors: Koutsilieri S, Tzioufa F, Sismanoglou DC, Patrinos GP

Abstract
Pharmacogenomics and personalized medicine interventions hold promise to optimize drug treatment modalities and hence, improve the quality of life of the patients by minimizing the occurrence of adverse drug reactions and/or maximizing drug treatment efficacy. To this end, proper guidance for accurately prescribing the correct drug at the right dose is empowered by major regulatory bodies, namely the U.S. Food and Drug Administration (FDA) and the European Medicine Agency (EMA), and well-recognized research consortia, like the Clinical Pharmacogenetics Implementation Consortium (CPIC), that propose therapeutic recommendations after the thorough evaluation of the existing scientific evidence base. In this context, the consistency of these recommendations is crucial for smoothly integrating pharmacogenomics into the clinic. Here, we collected all of the important and clinically actionable pharmacogenomic information provided by the aforementioned renowned sources and documented it in order to assess potential similarities and, most importantly, differences. Our data show that the level of concordance regarding the guidance provided for the same drug-gene association pairs varies significantly, despite the fact that it all derives from a single evidence base. In particular, apart from the expected similarities in a number of association pairs, especially the ones related to cancer genomics, there are still major discrepancies that create confusion as to which guidance should be followed in order to properly inform drug prescribing. This regulatory deficiency calls for the fruitful engagement of the regulatory agencies involved with the contribution of other experts engaged in the field of pharmacogenomics in an effort to harmonize the existing arsenal of guidelines for genome-informed drug prescription. The achievement of harmonization would in turn expedite bringing personalized medicine closer to clinical fruition.

PMID: 31830522 [PubMed - as supplied by publisher]

Long-term efficacy of metformin in obese PCOS: longitudinal follow up of retrospective cohort.

Endocr Connect. 2019 Dec 01;:

Authors: Jensterle M, Kravos NA, Ferjan S, Goricar K, Dolzan V, Janez A

Abstract
OBJECTIVE: Long-term efficacy of metformin in polycystic ovarian syndrome (PCOS) apart from in those with impaired glucose tolerance or diabetes remains unproven. We aimed to evaluate the impact of metformin in overweight-obese patients with PCOS and normal baseline glycemic homeostasis.
METHODS: 10 year longitudinal follow up of retrospective cohort comprising of 159 patients with PCOS defined by Rotterdam criteria, BMI≥ 25kg/m2 and normal initial glucose homeostasis (age 28.4±6.4 years, BMI 34.9±6.6 kg/m2) that had been receiving metformin 1000 mg BID. Collection data contained 6085time-points including anthropometric, hormonal and metabolic parameters.
RESULTS: After the 1st year body mass(BM) decreased for 3,9±6.8kg (p<0.001) and remained stable during the following 3 years. Menstrual frequency (MF) increased for3.0±3.9 bleeds/year (p<0.001) after 1st year to over 11 bleeds/year in the following years. The total testosterone and androstenedione decreased for 15.4±47.9% and 11.3±46.4% within 1st year, with further decrease in total testosterone and androstenedione for 37.8±61.8 and 24.8±40.5% at the 5th year of the follow up. The total conversion rate to prediabetes and diabetes was extremely low throughout observation period. Less than 25% of patients continued with metformin for more than five years with further dropout to only 6% on metformin therapy at the 10th year of follow up.
CONCLUSIONS: Long-term metformin treatment of overweight-obese women with PCOS and normal baseline glycemic homeostasis resulted in reduction and stabilization of BM, improvements of MF and androgen profile and low conversion rate to diabetes.

PMID: 31829964 [PubMed - as supplied by publisher]

Circulating tumor DNA (ctDNA) in precision oncology of ovarian cancer.

Pharmacogenomics. 2019 Dec;20(18):1251-1253

Authors: Oikkonen J, Hautaniemi S

PMID: 31829836 [PubMed - in process]

Circulating tumor DNA and the future of EGFR-mutant lung cancer treatment.

Pharmacogenomics. 2019 Dec;20(18):1255-1257

Authors: Re MD, Addeo A, Passaro A, Petrini I, van Schaik RH, Danesi R

PMID: 31829835 [PubMed - in process]

Effects of pharmacogenetic variants on vemurafenib-related toxicities in patients with melanoma.

Pharmacogenomics. 2019 Dec;20(18):1283-1290

Authors: Goey AK, With M, Agema BC, Hoop EO, Singh RK, van der Veldt AA, Mathijssen RH, van Schaik RH, Bins S

Abstract
Aim: The pharmacokinetics and pharmacodynamics of vemurafenib are characterized by a wide interpatient variability. Since multiple polymorphic enzymes and drug transporters are involved in vemurafenib pharmacokinetics, we studied associations of polymorphisms on vemurafenib-associated toxicities. Patients & methods: Prospectively collected samples of 97 melanoma patients treated with vemurafenib alone (n = 62) or in combination with cobimetinib (n = 35) were genotyped for ABCB1 (3435C>T), ABCG2 (421C>A, 34G>A) and CYP3A4 (*22, 15389C>T) polymorphisms. Associations between these variants and the incidence of toxicities were studied. Results: CYP3A4*22 was significantly associated with increased risk for grade ≥3 nausea, grade 1-4 hyperbilirubinemia, and cutaneous squamous cell carcinoma. ABCB1 3435C>T was a predictor for grade ≥3 toxicity. Conclusion: Genetic variants in CYP3A4 and ABCB1 are associated with vemurafenib-associated toxicities.

PMID: 31829834 [PubMed - in process]

A Deep Learning Framework for Predicting Response to Therapy in Cancer.

Cell Rep. 2019 Dec 10;29(11):3367-3373.e4

Authors: Sakellaropoulos T, Vougas K, Narang S, Koinis F, Kotsinas A, Polyzos A, Moss TJ, Piha-Paul S, Zhou H, Kardala E, Damianidou E, Alexopoulos LG, Aifantis I, Townsend PA, Panayiotidis MI, Sfikakis P, Bartek J, Fitzgerald RC, Thanos D, Mills Shaw KR, Petty R, Tsirigos A, Gorgoulis VG

Abstract
A major challenge in cancer treatment is predicting clinical response to anti-cancer drugs on a personalized basis. Using a pharmacogenomics database of 1,001 cancer cell lines, we trained deep neural networks for prediction of drug response and assessed their performance on multiple clinical cohorts. We demonstrate that deep neural networks outperform the current state in machine learning frameworks. We provide a proof of concept for the use of deep neural network-based frameworks to aid precision oncology strategies.

PMID: 31825821 [PubMed - in process]

Recent advances in understanding of attention deficit hyperactivity disorder (ADHD): how genetics are shaping our conceptualization of this disorder.

F1000Res. 2019;8:

Authors: Zayats T, Neale BM

Abstract
Attention deficit hyperactivity disorder (ADHD) is a clinically defined disorder, and inattention and hyperactivity/impulsivity are its main symptom domains. The presentation, lifelong continuation and treatment response of ADHD symptoms, however, is highly heterogeneous. To better define, diagnose, treat and prevent ADHD, it is essential that we understand the biological processes underlying all of these elements. In this review, given the high heritability of ADHD, we discuss how and why genetics can foster such progress. We examine what genetics have taught us so far with regard to ADHD definition, classification, clinical presentation, diagnosis and treatment. Finally, we offer a prospect of what genetic studies on ADHD may bring in the future.

PMID: 31824658 [PubMed - in process]

Fear not: recent advances in understanding the neural basis of fear memories and implications for treatment development.

F1000Res. 2019;8:

Authors: Milton AL

Abstract
Fear is a highly adaptive emotion that has evolved to promote survival and reproductive fitness. However, maladaptive expression of fear can lead to debilitating stressor-related and anxiety disorders such as post-traumatic stress disorder. Although the neural basis of fear has been extensively researched for several decades, recent technological advances in pharmacogenetics and optogenetics have allowed greater resolution in understanding the neural circuits that underlie fear. Alongside conceptual advances in the understanding of fear memory, this increased knowledge has clarified mechanisms for some currently available therapies for post-traumatic stress disorder and has identified new potential treatment targets.

PMID: 31824654 [PubMed - in process]

Informing Integration of Genomic Medicine Into Primary Care: An Assessment of Current Practice, Attitudes, and Desired Resources.

Front Genet. 2019;10:1189

Authors: Carroll JC, Allanson J, Morrison S, Miller FA, Wilson BJ, Permaul JA, Telner D

Abstract
Introduction: Preparing primary care providers for genomic medicine (GM) first requires assessment of their educational needs in order to provide clear, purposeful direction and justify educational activities. More understanding is needed about primary care providers' perspectives on their role in newer areas of GM and what resources would be helpful in practice. Our objective was to determine family physicians' (FP) current involvement and confidence in GM, attitudes regarding its clinical value, suggestions for integration of GM into practice, and resources and education required. Methods: A self-complete anonymous questionnaire was mailed to a random sample of 2,000 FPs in Ontario, Canada in September 2012. Results: Adjusted response rate was 26% (361/1,365), mean age was 51, and 53% were male. FPs reported many aspects of traditional GM as part of current practice (eliciting family history: 93%; deciding who to refer to genetics: 94%; but few reported confidence (44%, 32% respectively). Newer areas of GM were not part of most FPs' current practice and confidence was low (pharmacogenetics: 28% part of practice, 5% confident; direct-to-consumer genetic testing: 14%/2%; whole genome sequencing: 8%/2%). Attitudes were mixed with 59% agreeing that GM would improve patient health outcomes, 41% seeing benefits to genetic testing, but only 36% agreeing it was their responsibility to incorporate GM into practice. Few could identify useful sources of genetic information (22%) or find information about genetic tests (21%). Educational resources participants anticipated would be useful included contact information for local genetics clinics (89%), summaries of genetic disorders (86%), and genetic referral (85%) and testing (86%) criteria. About 58% were interested in learning about new genetic technologies. Most (76%) wanted to learn through in-person teaching (lectures, seminars etc.), 66% wanted contact with a local genetic counselor to answer questions, and 59% were interested in a genetics education website. Conclusion: FPs lack confidence in GM skills needed for practice, particularly in emerging areas of GM. They see their role as making appropriate referrals, are somewhat optimistic about the contribution GM may make to patient care, but express caution about its current clinical benefits. There is a need for evidence-based educational resources integrated into primary care and improved communication with genetic specialists.

PMID: 31824576 [PubMed]

The multi-faceted functioning portrait of LRF/ZBTB7A.

Hum Genomics. 2019 Dec 10;13(1):66

Authors: Constantinou C, Spella M, Chondrou V, Patrinos GP, Papachatzopoulou A, Sgourou A

Abstract
Transcription factors (TFs) consisting of zinc fingers combined with BTB (for broad-complex, tram-track, and bric-a-brac) domain (ZBTB) are a highly conserved protein family that comprises a multifunctional and heterogeneous group of TFs, mainly modulating cell developmental events and cell fate. LRF/ZBTB7A, in particular, is reported to be implicated in a wide variety of physiological and cancer-related cell events. These physiological processes include regulation of erythrocyte maturation, B/T cell differentiation, adipogenesis, and thymic insulin expression affecting consequently insulin self-tolerance. In cancer, LRF/ZBTB7A has been reported to act either as oncogenic or as oncosuppressive factor by affecting specific cell processes (proliferation, apoptosis, invasion, migration, metastasis, etc) in opposed ways, depending on cancer type and molecular interactions. The molecular mechanisms via which LRF/ZBTB7A is known to exert either physiological or cancer-related cellular effects include chromatin organization and remodeling, regulation of the Notch signaling axis, cellular response to DNA damage stimulus, epigenetic-dependent regulation of transcription, regulation of the expression and activity of NF-κB and p53, and regulation of aerobic glycolysis and oxidative phosphorylation (Warburg effect). It is a pleiotropic TF, and thus, alterations to its expression status become detrimental for cell survival. This review summarizes its implication in different cellular activities and the commonly invoked molecular mechanisms triggered by LRF/ZBTB7A's orchestrated action.

PMID: 31823818 [PubMed - in process]

Genetic variation in EPHA contributes to sensitivity to paclitaxel-induced peripheral neuropathy.

Br J Clin Pharmacol. 2019 Dec 10;:

Authors: Marcath LA, Kidwell KM, Vangipuram K, Gersch CL, Rae JM, Burness ML, Griggs JJ, Van Poznak C, Hayes DF, Lavoie Smith EM, Henry NL, Beutler AS, Hertz DL

Abstract
AIMS: Chemotherapy-induced peripheral neuropathy (PN) is a treatment limiting toxicity of paclitaxel. We evaluated if EPHA genetic variation (EPHA4, EPHA5, EPHA6, and EPHA8) is associated with PN sensitivity by accounting for variability in systemic paclitaxel exposure (time above threshold).
METHODS: Germline DNA from 60 patients with breast cancer was sequenced. PN was measured using the 8-item sensory subscale (CIPN8) of the patient-reported CIPN20. Associations for three genetic models were tested by incorporating genetics into previously published PN prediction models integrating measured paclitaxel exposure and cumulative treatment. Significant associations were then tested for association with PN-related treatment disruption.
RESULTS: EPHA5 rs7349683 (minor allele frequency=0.32) was associated with increased PN sensitivity (ß-coefficient=0.39, 95% confidence interval (CI) 0.11-0.67, p=0.007). Setting a maximum tolerable threshold of CIPN8=30, optimal paclitaxel exposure target is shorter for rs7349683 homozygous (11.6 hrs) than heterozygous (12.6 hrs) or wild-type (13.6 hrs) patients. Total number of missense variants (median=0, range 0-2) was associated with decreased PN sensitivity (beta coefficient: -0.42, 95% CI -0.72 - -0.12, p=0.006). No association with treatment disruption was detected for the total number of missense variants and rs7349683.
CONCLUSIONS: Isolating toxicity sensitivity by accounting for exposure is a novel approach, and rs7349683 represents a promising marker for PN sensitivity that may be used to individualize paclitaxel treatment.

PMID: 31823378 [PubMed - as supplied by publisher]

Human genetics and genomics research in Ecuador: historical survey, current state, and future directions.

Hum Genomics. 2019 Dec 10;13(1):64

Authors: Zambrano-Mila MS, Agathos SN, Reichardt JKV

Abstract
BACKGROUND: In South America, the history of human genetics is extensive and its beginnings go back to the onset of the twentieth century. In Ecuador, the historical record of human genetics and genomics research is limited. In this context, our work analyzes the current status and historical panorama of these fields, based on bibliographic searches in Scopus, Google Scholar, PubMed, and Web of Science.
RESULTS: Our results determined that the oldest paper in human genetics coauthored by an Ecuadorian institution originates from the Central University of Ecuador in 1978. From a historical standpoint, the number of articles has increased since the 1990s. This growth has intensified and it is reflected in 137 manuscripts recorded from 2010 to 2019. Areas such as human population genetics, phylogeography, and forensic sciences are the core of genetics and genomics-associated research in Ecuador. Important advances have been made in the understanding of the bases of cancer, some genetic diseases, and congenital disorders. Fields such as pharmacogenetics and pharmacogenomics have begun to be explored during the last years.
CONCLUSIONS: This work paints a comprehensive picture and provides additional insights into the future panorama of human genetic and genomic research in Ecuador as an example of an emerging, resource-limited country with interesting phylogeographic characteristics and public health implications.

PMID: 31822297 [PubMed - in process]

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Pharmacogenomic phase transition from personalized medicine to patient-centric customized delivery.

Pharmacogenomics J. 2019 Dec 10;:

Authors: Radhakrishnan A, Kuppusamy G, Ponnusankar S, Shanmukhan NK

Abstract
Personalized medicine has been a booming area in clinical research for the past decade, in which the detailed information about the patient genotype and clinical conditions were collected and considered to optimize the therapy to prevent adverse reactions. However, the utility of commercially available personalized medicine has not yet been maximized due to the lack of a structured protocol for implementation. In this narrative review, we explain the role of pharmacogenetics in personalized medicine, next-generation personalized medicine, i.e., patient-centric personalized medicine, in which the patient's comfort is considered along with pharmacogenomics to be a primary factor. We extensively discuss the classifications, strategies, tools, and drug delivery systems that can support the implementation of patient-centric personalized medicine from an industrial perspective.

PMID: 31819163 [PubMed - as supplied by publisher]