[Effect of polymorphisms of NF-κB and PXR on platinum-based chemotherapy for non-small cell lung cancer].

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2016 Mar 28;41(3):233-7

Authors: Zhou Y, Yang P, Liu Y, Wang L

Abstract
OBJECTIVE: To investigate the effect of polymorphisms of NF-κB rs230521, NF-κB rs4648068 and pregnane X receptor (PXR) rs3814058 on platinum-based chemotherapy for non-small cell lung cancer patients. 

METHODS: We collected 262 cases of non-small cell lung cancer patients, and then analyzed the genotypes of NF-κB and PXR by MassARRAY method. The impact of polymorphisms on efficacy, gastrointestinal toxicity and hematological toxicity was analyzed by logistic regression.

RESULTS: Compared to patients with GG genotype, patients with NF-κB rs230521 CC genotype had the higher risk to suffer hematological toxicity (OR=3.485, P=0.011). Patients with PXR rs3814058 CC and CT genotype exhibited higher possibility to suffer hematological toxicity than those with TT (OR=2.045, P=0.048). Polymorphism of NF-κB rs4648068 did not show significant effect on chemotherapy efficacy and occurrence of gastrointestinal toxicity and hematological toxicity.

CONCLUSION: Patients with NF-κB rs230521 CC, PXR rs3814058 CC and CT had higher risk to suffer hematological toxicity during platinum-based chemotherapy for non-small cell lung cancer. A rational dosage and course of treatment should be chosen to protect the patients with high risk genotype suffering hematological toxicity during their platinum-based therapy.

PMID: 27033785 [PubMed - indexed for MEDLINE]

Pharmacogenomics study on cadherin 2 network with regard to HIV infection and methadone treatment outcome.

PLoS One. 2017;12(3):e0174647

Authors: Kuo HW, Shih CL, Tsung JH, Liu SW, Chu SK, Yang HC, Tsou HH, Wang ZH, Chen AC, Liu YL

Abstract
Heroin dependent patients have a high incidence of HIV infection. In contrast to the gene expression method, we developed a systemic correlation analysis method built upon the results of pharmacogenomics study in a methadone maintenance treatment (MMT) cohort consisting of 344 Taiwanese heroin dependent patients. We identified genetic variants and their encoding proteins that may be involved with HIV infection and MMT treatment outcome. Cadherin 2 (CDH2) genetic determinants were identified through the genome-wide pharmacogenomic study. We found significant correlations among HIV infection status, plasma levels of CDH2, cytokine IL-7, ADAM10, and the treatment responses to methadone. Two single nucleotide polymorphisms located within CDH2 gene showed associations with blood pressure and plasma CDH2 concentration. Plasma concentration of CDH2 showed correlations with the level of cytokine IL-7, status of HIV infection, and urine morphine test result. Plasma level of IL-7 was correlated with corrected QT interval (QTc) and gooseflesh skin withdrawal symptom score, while level of ADAM10 was correlated with plasma concentrations of vitamin D metabolite, nicotine metabolite, and R-methadone. The results suggest a novel network involving HIV infection and methadone treatment outcome.

PMID: 28358908 [PubMed - in process]

Pharmacogenetics in the treatment of pre-eclampsia: current findings, challenges and perspectives.

Pharmacogenomics. 2017 Mar 30;:

Authors: Luizon MR, Palei AC, Cavalli RC, Sandrim VC

Abstract
Pre-eclampsia (PE) is defined as pregnancy-induced hypertension and proteinuria, and is a major cause of maternal and perinatal morbidity and mortality. A large subgroup of pregnant women with PE is nonresponsive to antihypertensive drugs, including methyldopa, nifedipine and hydralazine. Pharmacogenomics may help to guide the individualized therapy for this nonresponsive subgroup. However, just a few pharmacogenetic studies examined the effects of genetic polymorphisms on response to antihypertensive drugs in PE, and the criteria of responsiveness used to define responsive or nonresponsive subgroups to antihypertensive therapy should be replicated by others. We review these gene-drugs interactions, novel approaches to pharmacogenomics research and potential novel drugs for PE therapy. Finally, we discuss the challenges and perspectives of pharmacogenetics in the treatment of PE.

PMID: 28358601 [PubMed - as supplied by publisher]

Common genetic polymorphisms of adenosine A2A receptor do not influence response to regadenoson.

Pharmacogenomics. 2017 Mar 30;:

Authors: Berlacher M, Mastouri R, Philips S, Skaar TC, Kreutz RP

Abstract
AIM: Hemodynamic response to regadenoson varies greatly, and underlying mechanisms for variability are poorly understood. We hypothesized that five common variants of adenosine A2A receptor (ADORA2A) are associated with altered response to regadenoson.
METHODS: Consecutive subjects (n = 357) undergoing resting regadenoson nuclear stress imaging were enrolled. Genotyping was performed using Taqman-based assays for rs5751862, rs229838, rs3761422, rs2267076 and rs5751876.
RESULTS: There was no significant difference in heart rate or blood pressure between different genotypes following regadenoson administration. There was also no significant difference in myocardial ischemia detected by nuclear perfusion imaging as defined by summed difference score, or in self-reported side effects among the genotypes tested.
CONCLUSION: The common A2A variants studied are not associated with variability in hemodynamic response to regadenoson or variability in detection of ischemia with nuclear perfusion stress imaging.

PMID: 28358597 [PubMed - as supplied by publisher]

HLA-B*15:21 and carbamazepine-induced Stevens-Johnson syndrome: pooled-data and in silico analysis.

Sci Rep. 2017 Mar 30;7:45553

Authors: Jaruthamsophon K, Tipmanee V, Sangiemchoey A, Sukasem C, Limprasert P

Abstract
HLA-B*15:02 screening before carbamazepine (CBZ) prescription in Asian populations is the recommended practice to prevent CBZ-induced Stevens-Johnson syndrome (CBZ-SJS). However, a number of patients have developed CBZ-SJS even having no HLA-B*15:02. Herein, we present the case of a Thai patient who had a negative HLA-B*15:02 screening result but later developed CBZ-SJS. Further HLA typing revealed HLA-B*15:21/B*13:01. HLA-B*15:21 is a member of the HLA-B75 serotype and is commonly found in Southeast Asian populations. Based on this case, we hypothesised that if all HLA-B*15:02 carriers were prevented from CBZ prescription, another common HLA-B75 serotype marker would show its association with CBZ-SJS. To test this hypothesis, we pooled data from previous association studies in Asian populations, excluded all cases with HLA-B*15:02, and analysed the association significance of HLA-B75 serotype markers. A significant association was found between CBZ-SJS and HLA-B*15:21 and HLA-B*15:11. We also applied an in silico analysis and found that all HLA-B75 serotype molecules shared similar capability in binding the CBZ molecule. In summary, this report provides the first evidence of a positive association between HLA-B*15:21 and CBZ-SJS and the first in silico analysis of CBZ binding sites and details of the molecular behaviour of HLA-B75 molecule to explain its molecular action.

PMID: 28358139 [PubMed - in process]

NLRP3 and CARD8 Polymorphisms Influence Higher Disease Activity in Rheumatoid Arthritis.

J Med Biochem. 2016 Sep;35(3):319-323

Authors: Jenko B, Praprotnik S, Tomšic M, Dolžan V

Abstract
BACKGROUND: The activation of NLRP3-inflammasome may contribute to inflammatory processes in rheumatoid arthritis (RA). Functional polymorphisms in the genes coding for its components NLRP3 and CARD8 were associated with a proinflammatory phenotype. Our aim was to investigate the influence of these polymorphisms on RA susceptibility and disease activity at the time of diagnosis and after six months of treatment.
METHODS: A group of 128 RA patients treated with methotrexate and 122 healthy controls were genotyped for NLRP3 rs35829419 (p. Q705K) and CARD8 rs2043211 (p. C10X) polymorphisms.
RESULTS: RA susceptibility was not influenced by the investigated polymorphisms or their interaction. The investigated polymorphisms explained 8% of variability in DAS28 at the time of diagnosis. Carriers of NLRP3 rs35829419 or CARD8 rs2043211 polymorphisms had significantly higher DAS28 at the time of diagnosis (p=0.003; p=0.022; respectively). Polymorphic CARD8 rs2043211 TT genotype was also associated with higher DAS28 after six months of treatment (p=0.033).
CONCLUSIONS: Genetic variability of inflammasome components may contribute to higher disease activity at the time of diagnosis and after 6 months of methotrexate treatment in RA patients. Better understanding of the immunological mechanisms behind a more active course of RA may suggest novel treatment approaches in a subset of patients with a proinflammatory phenotype.

PMID: 28356883 [PubMed - in process]

Drug-screening and genomic analyses of HER2-positive breast cancer cell lines reveal predictors for treatment response.

Breast Cancer (Dove Med Press). 2017;9:185-198

Authors: Jernström S, Hongisto V, Leivonen SK, Due EU, Tadele DS, Edgren H, Kallioniemi O, Perälä M, Mælandsmo GM, Sahlberg KK

Abstract
BACKGROUND: Approximately 15%-20% of all diagnosed breast cancers are characterized by amplified and overexpressed HER2 (= ErbB2). These breast cancers are aggressive and have a poor prognosis. Although improvements in treatment have been achieved after the introduction of trastuzumab and lapatinib, many patients do not benefit from these drugs. Therefore, in-depth understanding of the mechanisms behind the treatment responses is essential to find alternative therapeutic strategies.
MATERIALS AND METHODS: Thirteen HER2 positive breast cancer cell lines were screened with 22 commercially available compounds, mainly targeting proteins in the ErbB2-signaling pathway, and molecular mechanisms related to treatment sensitivity were sought. Cell viability was measured, and treatment responses between the cell lines were compared. To search for response predictors and genomic and transcriptomic profiling, PIK3CA mutations and PTEN status were explored and molecular features associated with drug sensitivity sought.
RESULTS: The cell lines were divided into three groups according to the growth-retarding effect induced by trastuzumab and lapatinib. Interestingly, two cell lines insensitive to trastuzumab (KPL4 and SUM190PT) showed sensitivity to an Akt1/2 kinase inhibitor. These cell lines had mutation in PIK3CA and loss of PTEN, suggesting an activated and druggable Akt-signaling pathway. Expression levels of five genes (CDC42, MAPK8, PLCG1, PTK6, and PAK6) were suggested as predictors for the Akt1/2 kinase-inhibitor response.
CONCLUSION: Targeting the Akt-signaling pathway shows promise in cell lines that do not respond to trastuzumab. In addition, our results indicate that several molecular features determine the growth-retarding effects induced by the drugs, suggesting that parameters other than HER2 amplification/expression should be included as markers for therapy decisions.

PMID: 28356768 [PubMed]

Overview of BioBank Japan follow-up data in 32 diseases.

J Epidemiol. 2017 Mar;27(3S):S22-S28

Authors: Hirata M, Nagai A, Kamatani Y, Ninomiya T, Tamakoshi A, Yamagata Z, Kubo M, Muto K, Kiyohara Y, Mushiroda T, Murakami Y, Yuji K, Furukawa Y, Zembutsu H, Tanaka T, Ohnishi Y, Nakamura Y, BioBank Japan Cooperative Hospital Group, Matsuda K

Abstract
BACKGROUND: We established a patient-oriented biobank, BioBank Japan, with information on approximately 200,000 patients, suffering from any of 47 common diseases. This follow-up survey focused on 32 diseases, potentially associated with poor vital prognosis, and collected patient survival information, including cause of death. We performed a survival analysis for all subjects to get an overview of BioBank Japan follow-up data.
METHODS: A total of 141,612 participants were included. The survival data were last updated in 2014. Kaplan-Meier survival analysis was performed after categorizing subjects according to sex, age group, and disease status. Relative survival rates were estimated using a survival-rate table of the Japanese general population.
RESULTS: Of 141,612 subjects (56.48% male) with 1,087,434 person-years and a 97.0% follow-up rate, 35,482 patients died during follow-up. Mean age at enrollment was 64.24 years for male subjects and 63.98 years for female subjects. The 5-year and 10-year relative survival rates for all subjects were 0.944 and 0.911, respectively, with a median follow-up duration of 8.40 years. Patients with pancreatic cancer had the least favorable prognosis (10-year relative survival: 0.184) and patients with dyslipidemia had the most favorable prognosis (1.013). The most common cause of death was malignant neoplasms. A number of subjects died from diseases other than their registered disease(s).
CONCLUSIONS: This is the first report to perform follow-up survival analysis across various common diseases. Further studies should use detailed clinical and genomic information to identify predictors of mortality in patients with common diseases, contributing to the implementation of personalized medicine.

PMID: 28190660 [PubMed - indexed for MEDLINE]

Cross-sectional analysis of BioBank Japan clinical data: A large cohort of 200,000 patients with 47 common diseases.

J Epidemiol. 2017 Mar;27(3S):S9-S21

Authors: Hirata M, Kamatani Y, Nagai A, Kiyohara Y, Ninomiya T, Tamakoshi A, Yamagata Z, Kubo M, Muto K, Mushiroda T, Murakami Y, Yuji K, Furukawa Y, Zembutsu H, Tanaka T, Ohnishi Y, Nakamura Y, BioBank Japan Cooperative Hospital Group, Matsuda K

Abstract
BACKGROUND: To implement personalized medicine, we established a large-scale patient cohort, BioBank Japan, in 2003. BioBank Japan contains DNA, serum, and clinical information derived from approximately 200,000 patients with 47 diseases. Serum and clinical information were collected annually until 2012.
METHODS: We analyzed clinical information of participants at enrollment, including age, sex, body mass index, hypertension, and smoking and drinking status, across 47 diseases, and compared the results with the Japanese database on Patient Survey and National Health and Nutrition Survey. We conducted multivariate logistic regression analysis, adjusting for sex and age, to assess the association between family history and disease development.
RESULTS: Distribution of age at enrollment reflected the typical age of disease onset. Analysis of the clinical information revealed strong associations between smoking and chronic obstructive pulmonary disease, drinking and esophageal cancer, high body mass index and metabolic disease, and hypertension and cardiovascular disease. Logistic regression analysis showed that individuals with a family history of keloid exhibited a higher odds ratio than those without a family history, highlighting the strong impact of host genetic factor(s) on disease onset.
CONCLUSIONS: Cross-sectional analysis of the clinical information of participants at enrollment revealed characteristics of the present cohort. Analysis of family history revealed the impact of host genetic factors on each disease. BioBank Japan, by publicly distributing DNA, serum, and clinical information, could be a fundamental infrastructure for the implementation of personalized medicine.

PMID: 28190657 [PubMed - indexed for MEDLINE]

Overview of the BioBank Japan Project: Study design and profile.

J Epidemiol. 2017 Mar;27(3S):S2-S8

Authors: Nagai A, Hirata M, Kamatani Y, Muto K, Matsuda K, Kiyohara Y, Ninomiya T, Tamakoshi A, Yamagata Z, Mushiroda T, Murakami Y, Yuji K, Furukawa Y, Zembutsu H, Tanaka T, Ohnishi Y, Nakamura Y, BioBank Japan Cooperative Hospital Group, Kubo M

Abstract
BACKGROUND: The BioBank Japan (BBJ) Project was launched in 2003 with the aim of providing evidence for the implementation of personalized medicine by constructing a large, patient-based biobank (BBJ). This report describes the study design and profile of BBJ participants who were registered during the first 5-year period of the project.
METHODS: The BBJ is a registry of patients diagnosed with any of 47 target common diseases. Patients were enrolled at 12 cooperative medical institutes all over Japan from June 2003 to March 2008. Clinical information was collected annually via interviews and medical record reviews until 2013. We collected DNA from all participants at baseline and collected annual serum samples until 2013. In addition, we followed patients who reported a history of 32 of the 47 target diseases to collect survival data, including cause of death.
RESULTS: During the 5-year period, 200,000 participants were registered in the study. The total number of cases was 291,274 at baseline. Baseline data for 199,982 participants (53.1% male) were available for analysis. The average age at entry was 62.7 years for men and 61.5 years for women. Follow-up surveys were performed for participants with any of 32 diseases, and survival time data for 141,612 participants were available for analysis.
CONCLUSIONS: The BBJ Project has constructed the infrastructure for genomic research for various common diseases. This clinical information, coupled with genomic data, will provide important clues for the implementation of personalized medicine.

PMID: 28189464 [PubMed - indexed for MEDLINE]

19 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2017/03/30

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30 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2017/03/28

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Pharmacogenomics and Patient Treatment Parameters to Opioid Treatment in Chronic Pain: A Focus on Morphine, Oxycodone, Tramadol, and Fentanyl.

Pain Med. 2017 Feb 24;:

Authors: Lloyd RA, Hotham E, Hall C, Williams M, Suppiah V

Abstract
Objective. : Opioids are one of the most commonly prescribed medicines for chronic pain. However, their use for chronic pain has been controversial. The objective of this literature review was to identify the role of genetic polymorphisms on patient treatment parameters (opioid dose requirements, response, and adverse effects) for opioids used in malignant and nonmalignant chronic pain. The opioids that this review focuses on are codeine, morphine, oxycodone, tramadol, and fentanyl.
Method. : A literature search of databases Medline and Embase was carried out, and studies up to April 2016 were included in this review. Studies were included based on a combination of key words: chronic pain and related terms, pharmacogenetics and related terms, and opioids and related terms.
Results. : Among the 1,408 individual papers retrieved from the search in Medline and Embase, 32 original articles were included in this review, with none related to codeine. The 32 papers reported various study designs, opioids, and polymorphisms being studied for associations with treatment outcomes. This literature review reveals that variants in ABCB1 , OPRM1 , and COMT have been replicated for opioid dosing and variants in ABCB1 have been replicated for both treatment response and adverse effects.
Conclusions. : Currently, there are few validated studies to form a strong evidence base to support pharmacogenomics testing when initiating opioid therapy. However, the field of pharmacogenomics in chronic pain is likely to expand over the coming years, with the increasing number of treatment options available and larger cohorts being assembled in order to identify true associations.

PMID: 28339912 [PubMed - as supplied by publisher]

Design and evaluation of a pharmacogenomics information resource for pharmacists.

J Am Med Inform Assoc. 2017 Feb 26;:

Authors: Romagnoli KM, Boyce RD, Empey PE, Ning Y, Adams S, Hochheiser H

Abstract
Objective: To develop and evaluate a pharmacogenomics information resource for pharmacists.
Materials and Methods: We built a pharmacogenomics information resource presenting Food and Drug Administration (FDA) drug product labelling information, refined it based on feedback from pharmacists, and conducted a comparative usability evaluation, measuring task completion time, task correctness and perceived usability. Tasks involved hypothetical clinical situations requiring interpretation of pharmacogenomics information to determine optimal prescribing for specific patients.
Results: Pharmacists were better able to perform certain tasks using the redesigned resource relative to the Pharmacogenomic Knowledgebase (PharmGKB) and the FDA Table of Pharmacogenomic Biomarkers in Drug Labeling. On average, participants completed tasks in 107.5 s using our resource, compared to 188.9 s using PharmGKB and 240.2 s using the FDA table. Using the System Usability Scale, participants rated our resource 79.62 on average, compared to 53.27 for PharmGKB and 50.77 for the FDA table. Participants found the correct answers for 100% of tasks using our resource, compared to 76.9% using PharmGKB and 69.2% using the FDA table.
Discussion: We present structured, clinically relevant pharmacogenomic FDA drug product label information with visualizations to help explain the relationships between gene variants, drugs, and phenotypes. The results from our evaluation suggest that user-centered interfaces for pharmacogenomics information can increase ease of access and comprehension.
Conclusion: A clinician-focused pharmacogenomics information resource can answer pharmacogenomics-related medication questions faster, more correctly, and more easily than widely used alternatives, as perceived by pharmacists.

PMID: 28339805 [PubMed - as supplied by publisher]

BRIDG: a domain information model for translational and clinical protocol-driven research.

J Am Med Inform Assoc. 2017 Feb 26;:

Authors: Becnel LB, Hastak S, Ver Hoef W, Milius RP, Slack M, Wold D, Glickman ML, Brodsky B, Jaffe C, Kush R, Helton E

Abstract
Background: It is critical to integrate and analyze data from biological, translational, and clinical studies with data from health systems; however, electronic artifacts are stored in thousands of disparate systems that are often unable to readily exchange data.
Objective: To facilitate meaningful data exchange, a model that presents a common understanding of biomedical research concepts and their relationships with health care semantics is required. The Biomedical Research Integrated Domain Group (BRIDG) domain information model fulfills this need. Software systems created from BRIDG have shared meaning "baked in," enabling interoperability among disparate systems. For nearly 10 years, the Clinical Data Standards Interchange Consortium, the National Cancer Institute, the US Food and Drug Administration, and Health Level 7 International have been key stakeholders in developing BRIDG.
Methods: BRIDG is an open-source Unified Modeling Language-class model developed through use cases and harmonization with other models.
Results: With its 4+ releases, BRIDG includes clinical and now translational research concepts in its Common, Protocol Representation, Study Conduct, Adverse Events, Regulatory, Statistical Analysis, Experiment, Biospecimen, and Molecular Biology subdomains.
Interpretation: The model is a Clinical Data Standards Interchange Consortium, Health Level 7 International, and International Standards Organization standard that has been utilized in national and international standards-based software development projects. It will continue to mature and evolve in the areas of clinical imaging, pathology, ontology, and vocabulary support. BRIDG 4.1.1 and prior releases are freely available at https://bridgmodel.nci.nih.gov .

PMID: 28339791 [PubMed - as supplied by publisher]

Pharmacokinetics, Pharmacodynamics, Pharmacogenomics, Safety, and Tolerability of Avatrombopag in Healthy Japanese and White Subjects.

Clin Pharmacol Drug Dev. 2017 Mar 24;:

Authors: Nomoto M, Pastino G, Rege B, Aluri J, Ferry J, Han D

Abstract
Avatrombopag, an orally administered, small-molecule thrombopoietin receptor (c-Mpl) agonist, is currently in clinical development for the potential treatment of severe thrombocytopenia in patients with chronic liver disease undergoing an elective procedure. The objectives of this study were to characterize and compare the pharmacokinetics (including the food effect) and pharmacodynamics (platelet count) of avatrombopag following single doses in Japanese and white subjects. Following single dosing under fasted and fed conditions, mean peak concentrations occurred at 5 to 8 hours and subsequently declined with a half-life of 16 to 18 hours in Japanese and white subjects. Administration with food did not alter the rate or extent of avatrombopag absorption but substantially reduced pharmacokinetic variability relative to the fasted state. CYP2C9 polymorphism (*2, *3) was associated with higher pharmacokinetic variability but not with any clinically important effect on variability in platelet response. Plasma exposures of avatrombopag increased in a dose-proportional manner over the dose range tested. After a single dose, platelet count increased in a dose-related manner, reaching a maximum by day 11 and returning to baseline levels by day 27. No clinically important differences were found when avatrombopag pharmacokinetics and pharmacodynamics were compared between Japanese and white subjects. Administration of avatrombopag was generally well tolerated.

PMID: 28339166 [PubMed - as supplied by publisher]

Pharmacokinetic and Pharmacodynamic Responses to Clopidogrel: Evidences and Perspectives.

Int J Environ Res Public Health. 2017 Mar 14;14(3):

Authors: Zhang YJ, Li MP, Tang J, Chen XP

Abstract
Clopidogrel has significantly reduced the incidence of recurrent atherothrombotic events in patients with acute coronary syndrome (ACS) and in those undergoing percutaneous coronary intervention (PCI). However, recurrence events still remain, which may be partly due to inadequate platelet inhibition by standard clopidogrel therapy. Genetic polymorphisms involved in clopidogrel's absorption, metabolism, and the P2Y12 receptor may interfere with its antiplatelet activity. Recent evidence indicated that epigenetic modification may also affect clopidogrel response. In addition, non-genetic factors such as demographics, disease complications, and drug-drug interactions can impair the antiplatelet effect of clopidogrel. The identification of factors contributing to the variation in clopidogrel response is needed to improve platelet inhibition and to reduce risk for cardiovascular events. This review encompasses the most recent updates on factors influencing pharmacokinetic and pharmacodynamic responses to clopidogrel.

PMID: 28335443 [PubMed - in process]

Pomegranate juice does not affect the disposition of simvastatin in healthy subjects.

Eur J Drug Metab Pharmacokinet. 2016 Aug;41(4):339-44

Authors: Park SJ, Yeo CW, Shim EJ, Kim H, Liu KH, Shin JG, Shon JH

Abstract
Previous in vitro and in vivo investigations reported controversial results for the inhibitory potential of pomegranate on Cytochrome P450 (CYP) 3A activity. This study evaluated the effect of pomegranate juice on the disposition of simvastatin, a CYP3A4 substrate, and simvastatin acid, its active metabolite, compared with grapefruit juice in healthy subjects. A single oral pharmacokinetic study of 40 mg simvastatin was conducted as a three-way crossover (control, pomegranate, and grapefruit juices) in 12 healthy male subjects. The subjects took pomegranate or grapefruit juice three times per day for 3 days (900 mL/day) and on the third day, the pharmacokinetic study was executed. Blood samples were collected to 24 h post-dose and the pharmacokinetic parameters of simvastatin and simvastatin acid were compared among the study periods. In the period of grapefruit juice, the mean C max and AUCinf of simvastatin [the geometric mean ratio (90 % CI) 15.6 (11.6-21.0) and 9.1 (6.0-13.7)] were increased significantly when compared with the control period, whereas they were not significantly different in the period of pomegranate juice [C max and AUCinf 1.20 (0.89-1.62) and 1.29 (0.85-1.94)]. The mean C max and AUCinf of simvastatin acid were increased significantly after intake of grapefruit juice, but not pomegranate juice. These results suggest that pomegranate juice affects little on the disposition of simvastatin in humans. Pomegranate juice does not seem to have a clinically relevant inhibitory potential on CYP3A4 activity.

PMID: 25720525 [PubMed - indexed for MEDLINE]

A review of connectivity map and computational approaches in pharmacogenomics.

Brief Bioinform. 2017 Feb 23;:

Authors:

PMID: 28334173 [PubMed - as supplied by publisher]

rs7968606 polymorphism of ANKS1B is associated with improvement in the PANSS general score of schizophrenia caused by amisulpride.

Hum Psychopharmacol. 2017 Mar 23;:

Authors: Kang SG, Chee IS, Lee K, Lee J

Abstract
A recent genome-wide pharmacogenomics study showed that the rs7968606 single-nucleotide polymorphism (SNP) of the ankyrin repeat and sterile alpha motif domain-containing protein 1B (ANKS1B) gene approached the threshold of statistical significance. The aim of this study was to determine the association between the rs7968606 SNP of ANKS1B and the treatment response to amisulpride in schizophrenia patients. In total, 154 participants were enrolled from six university hospitals in Korea. All the subjects were interviewed before and after 6 weeks of amisulpride treatment with the aid of the positive and negative syndrome scale and the clinical global impression-severity scale. Genotyping for the rs7968606 SNP of ANKS1B was performed in 101 subjects. Both the decrease (t = -2.067, p = 0.041) and improvement rate (t = -1.990, p = 0.049) in the positive and negative syndrome scale general score differed significantly between T-allele carriers and noncarriers of this polymorphism after 6 weeks of amisulpride treatment. To the best of our knowledge, this is the first genetic association study of the relationship between the rs7968606 SNP of ANKS1B and the response of schizophrenia patients to treatment with amisulpride. Future larger-scale studies involving more SNPs of ANKS1B will improve the understanding of the pharmacogenetics underlying the treatment responses to amisulpride.

PMID: 28332719 [PubMed - as supplied by publisher]