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

Pharmacogenomics[Title/Abstract]

These pubmed results were generated on 2016/12/28

PubMed comprises more than 24 million 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.

Pharmacogenomic Study Reveals New Variants of Drug Metabolizing Enzyme and Transporter Genes Associated with Steady-State Plasma Concentrations of Risperidone and 9-Hydroxyrisperidone in Thai Autism Spectrum Disorder Patients.

Front Pharmacol. 2016;7:475

Authors: Medhasi S, Pinthong D, Pasomsub E, Vanwong N, Ngamsamut N, Puangpetch A, Chamnanphon M, Hongkaew Y, Pratoomwun J, Limsila P, Sukasem C

Abstract
The present study sought to investigate the genetic variants in drug metabolizing enzyme and transporter (DMET) genes associated with steady-state plasma concentrations of risperidone among Thai autism spectrum disorder (ASD) patients. ASD patients taking risperidone for at least 1 month were enrolled for this pharmacogenomic study. Genotyping profile was obtained using Affymetrix DMET Plus array interrogating 1931 variants in 231 genes. Steady-state plasma risperidone and 9-hydroxyrisperidone were measured using liquid chromatography/tandem mass spectrometry assay. The final analysis included 483 markers for 167 genes. Six variants, ABCB11 (c.3084A > G, c.(∗)420A > G, c.(∗)368G > A, and c.(∗)236G > A) and ADH7 (c.690G > A and c.-5360G > A), were found to be associated with plasma concentrations of risperidone. 9-Hydroxyrisperidone and the total active-moiety levels were associated with six gene variants, SCLO1B1 (c.-11187G > A and c.521T > C), SLCO1B3 (c.334G > T, c.699A > G, and c.1557G > A), and SLC7A5 c.(∗)438C > G. Polymorphisms in UGT2B4 c.(∗)448A > G and CYP2D6 (c.1661G > C, c.4180G > C, and c.-2178G > A) showed considerable but not significant associations with metabolic ratio. This pharmacogenomic study identifies new genetic variants of DMET genes in monitoring risperidone therapy.

PMID: 28018217 [PubMed]

Review of Toxic Epidermal Necrolysis.

Int J Mol Sci. 2016 Dec 18;17(12):

Authors: Harris V, Jackson C, Cooper A

Abstract
Toxic epidermal necrolysis (TEN) is a rare but life threatening mucocutaneous reaction to drugs or their metabolites. It is characterised by widespread keratinocyte apoptosis and sloughing of the skin, erosions of the mucous membranes, painful blistering, and severe systemic disturbance. The pathophysiology of TEN is incompletely understood. Historically, it has been regarded as a drug-induced immune reaction initiated by cytotoxic lymphocytes via a human leukocyte antigen (HLA)-restricted pathway. Several mediators have been identified as contributors to the cell death seen in TEN, including; granulysin, soluble Fas ligand, perforin/granzyme, tumour necrosis factor-α (TNF-α), and TNF-related apoptosis-inducing ligand. Currently, granulysin is accepted as the most important mediator of T cell proliferation. There is uncertainty around the accepted management of TEN. The lack of definitive management guidelines for TEN is explained in part by the rarity of the disease and its high mortality rate, which makes it difficult to conduct randomised control trials on emerging therapies. Developments have been made in pharmacogenomics, with numerous HLA alleles identified; however, these have largely been ethnically specific. These associations have translated into screening recommendations for Han Chinese.

PMID: 27999358 [PubMed - in process]

[Genomics of lung adenocarcinoma: pathogenetic significance and clinical applications.]

Recenti Prog Med. 2016 Dec;107(12):652-672

Authors: Palmirotta R, Acquafredda S, Argentiero A, Carella C, Lanotte L, Pappagallo N, Quaresmini D, Silvestris F

Abstract
Diagnostic and therapeutic approaches to non small cell lung cancer (NSCLC), especially adenocarcinoma, have recently undergone dramatic evolution according to the tremendous amount of molecular data collected on this cancer. In fact, the application of oncogenomics has identified novel molecular subtypes of NSCLC and led the way to diagnostic criteria based on the expression of specific genetic alterations that can provide prognostic and specific indications to the molecular targeted therapies. In NSCLC, several genes show "driver" molecular alterations that confer oncogenic potential to progenitor cells through the enrollment of metabolic pathways critical for cell proliferation and tumor development. On the other hand, clinical management of NSCLC with small molecules has undoubtedly provided optimistic results with both a significant increase in overall survival and reduction in therapy-related toxicity including relative complications. Thus, pharmacogenomics, as the newest tool for using the targeted therapy represents the most innovative approach for treatment of this cancer once the molecular aberrations are identified. In particular, the relative mutational status of several driver genes including EGFR, ALK, ROS1 and others, is directly correlated to a better response to thyrosin-kinase inhibitors. Furthermore, other therapeutic strategies with inhibitors of angiogenic receptors, PARP, histone-deacetylase, PI3K and HSP90, are intensively studied in pre-clinical models as well as in clinical trials for a potential adoption in clinical practice. The introduction of more advanced techniques for molecular profiling also allows to identify pathogenic variants of many other genes involved in the progression of lung adenocarcinoma with the aim to develop novel molecular targets for pharmacological research. In this review, we will revisit the current applications of oncogenomics in the diagnosis and treatment of this tumor.

PMID: 27997009 [PubMed - in process]

Pharmacogenetic variants associated with outcome in patients with advanced gastric cancer treated with fluoropyrimidine and platinum-based triplet combinations: a pooled analysis of three prospective studies.

Pharmacogenomics J. 2016 Dec 20;:

Authors: Meulendijks D, Rozeman EA, Cats A, Sikorska K, Joerger M, Deenen MJ, Beijnen JH, Schellens JH

Abstract
The main treatment for advanced gastric cancer is fluoropyrimidine and platinum-based chemotherapy. We investigated the clinical validitiy of 19 candidate pharmacogenetic variants in ENOSF1 (enolase superfamily member 1), TYMS, CDA, MTHFR, TYMP, DPYD, ERCC1, ERCC2, GSTP1, GSTT1, GSTM1, CYP3A4 and CYP3A5 in relation to overall survival (OS), progression-free survival, objective response rate (ORR) and toxicity in 185 patients receiving triplet chemotherapy. The formal significance threshold was P<0.0026. TYMS VNTR (variable number of 28-bp tandem repeats) 3 R/3 R genotype was formally associated with inferior ORR (odds ratio (OR) 0.3, P=0.0025), whereas ENOSF1 rs2612091 G/G was nominally associated with OS after adjustment for TYMS 3 R/3 R (hazard ratio (HR) 1.5, P=0.041). In a subgroup analysis of patients with locally advanced disease (n=33), ENOSF1 rs2612091 was strongly associated with OS (HR 6.5, P=0.001). CYP3A4*22/CYP3A5*3 genotype was nominally associated with grade 3/4 toxicity in patients receiving docetaxel-containing chemotherapy (P=0.0175). This is the first study suggesting that ENOSF1 rs2612091 is prognostic or predictive of OS in gastric cancer. This finding requires prospective validation.The Pharmacogenomics Journal advance online publication, 20 December 2016; doi:10.1038/tpj.2016.81.

PMID: 27995989 [PubMed - as supplied by publisher]

Network-guided modelling allows tumor-type independent prediction of sensitivity to all-trans retinoic acid.

Ann Oncol. 2016 Dec 19;:

Authors: Bolis M, Garattini E, Paroni G, Zanetti A, Kurosaki M, Castrignano' T, Garattini SK, Biancardi F, Barzago MM, Gianni' M, Terao M, Pattini L, Fratelli M

Abstract
BACKGROUND: All-trans retinoic acid (ATRA) is a differentiating agent used in the treatment of acute-promyelocytic-leukemia and it is under-exploited in other malignancies despite its low systemic toxicity. A rational/personalized use of ATRA requires development of predictive tools allowing identification of sensitive cancer types and responsive individuals.
MATERIALS AND METHODS: RNA-Sequencing data for 10080 patients and 33 different tumor-types were derived from the TCGA and Leucegene datasets and completely re-processed. The study was performed using machine learning methods and network analysis.
RESULTS: We profiled a large panel of breast-cancer cell-lines for in vitro sensitivity to ATRA and exploited the associated basal gene-expression data to initially generate a model predicting ATRA-sensitivity in this disease. Starting from these results and using a network-guided approach, we developed a generalized model (ATRA-21) whose validity extends to tumor-types other than breast cancer. ATRA-21 predictions correlate with experimentally determined sensitivity in a large panel of cell-lines representative of numerous tumor-types. In patients, ATRA-21 correctly identifies APL as the most sensitive acute-myelogenous-leukemia subtype and indicates that uveal-melanoma and low-grade glioma are top-ranking diseases as for average predicted responsiveness to ATRA. There is a consistent number of tumor-types for which higher ATRA-21 predictions are associated with better outcomes.
CONCLUSIONS: In summary, we generated a tumor-type independent ATRA-sensitivity predictor which consists of a restricted number of genes and has the potential to be applied in the clinics. Identification of the tumor-types which are likely to be generally sensitive to the action of ATRA paves the way to the design of clinical studies in the context of these diseases. In addition, ATRA-21 may represent an important diagnostic tool for the selection of individual patients who may benefit from ATRA-based therapeutic strategies also in tumors characterized by lower average sensitivity.

PMID: 27993792 [PubMed - as supplied by publisher]

Interview with Dr Ghassan K Abou-Alfa.

Immunotherapy. 2016 Nov;8(11):1277-1279

Authors: Abou-Alfa GK

Abstract
Ghassan K Abou-Alfa joined the Gastrointestinal Oncology Service at Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College in New York back in 2001. Dr Abou-Alfa specializes in the treatment of gastrointestinal malignancies. Dr Abou-Alfa received his medical degree from the American University of Beirut, Lebanon, and completed his post-doctoral training at Yale University School of Medicine. His research is dedicated to finding novel therapies and improving the effectiveness of the current therapies for hepatocellular carcinoma, cholangiocarcinoma and gallbladder cancer, while continuing to understand the basic mechanisms of the diseases and its therapy. Dr Abou-Alfa has invested several years in helping develop multi-tyrosine kinases and more immune-modulator therapies. Dr Abou-Alfa has many publications in the field. He led on many occasions international teams of investigators. Dr Abou-Alfa serves as the chair of the National Cancer Institute (NCI) Task Force for Hepatobiliary Cancers and the chair of the AIDS Malignancy Consortium (AMC) Non-AIDS Defining Malignancies (NADC) Liver/GI Task Force. Dr Abou-Alfa also co-chairs the hepatobiliary cancers subgroup of the Alliance cooperative group, and is a cadre member of both the gastrointestinal cancers and pharmacogenomics and population pharmacology committees. Dr Abou-Alfa who has lectured worldwide on the subject on gastrointestinal malignancies, is also a strong advocate for raising awareness and support for improving the outcome of patients with this disease, and enhancing oncologic education worldwide.

PMID: 27993088 [PubMed - in process]

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

Pharmacogenomics[Title/Abstract] AND ("2005/01/01"[PDAT] : "3000"[PDAT])

These pubmed results were generated on 2016/12/21

PubMed comprises more than 24 million 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.

The Impact of Genetic and Non-Genetic Factors on Warfarin Dose Prediction in MENA Region: A Systematic Review.

PLoS One. 2016;11(12):e0168732

Authors: Bader LA, Elewa H

Abstract
BACKGROUND: Warfarin is the most commonly used oral anticoagulant for the treatment and prevention of thromboembolic disorders. Pharmacogenomics studies have shown that variants in CYP2C9 and VKORC1 genes are strongly and consistently associated with warfarin dose variability. Although different populations from the Middle East and North Africa (MENA) region may share the same ancestry, it is still unclear how they compare in the genetic and non-genetic factors affecting their warfarin dosing.
OBJECTIVE: To explore the prevalence of CYP2C9 and VKORC1 variants in MENA, and the effect of these variants along with other non-genetic factors in predicting warfarin dose.
METHODS: In this systematic review, we included observational cross sectional and cohort studies that enrolled patients on stable warfarin dose and had the genetics and non-genetics factors associated with mean warfarin dose as the primary outcome. We searched PubMed, Medline, Scopus, PharmGKB, PHGKB, Google scholar and reference lists of relevant reviews.
RESULTS: We identified 17 studies in eight different populations: Iranian, Israeli, Egyptian, Lebanese, Omani, Kuwaiti, Sudanese and Turkish. Most common genetic variant in all populations was the VKORC1 (-1639G>A), with a minor allele frequency ranging from 30% in Egyptians and up to 52% and 56% in Lebanese and Iranian, respectively. Variants in the CYP2C9 were less common, with the highest MAF for CYP2C9*2 among Iranians (27%). Variants in the VKORC1 and CYP2C9 were the most significant predictors of warfarin dose in all populations. Along with other genetic and non-genetic factors, they explained up to 63% of the dose variability in Omani and Israeli patients.
CONCLUSION: Variants of VKORC1 and CYP2C9 are the strongest predictors of warfarin dose variability among the different populations from MENA. Although many of those populations share the same ancestry and are similar in their warfarin dose predictors, a population specific dosing algorithm is needed for the prospective estimation of warfarin dose.

PMID: 27992547 [PubMed - in process]

What is the future of pharmacogenomics in pain management?

Pharmacogenomics. 2016 Dec 19;

Authors: Peiró AM, Margarit C, LLerena A

PMID: 27992298 [PubMed - as supplied by publisher]

Current and future directions in the treatment and prevention of drug-induced liver injury: a systematic review.

Expert Rev Gastroenterol Hepatol. 2016;10(4):517-36

Authors: Stine JG, Lewis JH

Abstract
While the pace of discovery of new agents, mechanisms and risk factors involved in drug-induced liver injury (DILI) remains brisk, advances in the treatment of acute DILI seems slow by comparison. In general, the key to treating suspected DILI is to stop using the drug prior to developing irreversible liver failure. However, predicting when to stop is an inexact science, and commonly used ALT monitoring is an ineffective strategy outside of clinical trials. The only specific antidote for acute DILI remains N-acetylcysteine (NAC) for acetaminophen poisoning, although NAC is proving to be beneficial in some cases of non-acetaminophen DILI in adults. Corticosteroids can be effective for DILI associated with autoimmune or systemic hypersensitivity features. Ursodeoxycholic acid, silymarin and glycyrrhizin have been used to treat DILI for decades, but success remains anecdotal. Bile acid washout regimens using cholestyramine appear to be more evidenced based, in particular for leflunomide toxicity. For drug-induced acute liver failure, the use of liver support systems is still investigational in the United States and emergency liver transplant remains limited by its availability. Primary prevention appears to be the key to avoiding DILI and the need for acute treatment. Pharmacogenomics, including human leukocyte antigen genotyping and the discovery of specific DILI biomarkers offers significant promise for the future. This article describes and summarizes the numerous and diverse treatment and prevention modalities that are currently available to manage DILI.

PMID: 26633044 [PubMed - indexed for MEDLINE]

Long-Read Single Molecule Real-Time Full Gene Sequencing of Cytochrome P450-2D6.

Hum Mutat. 2016 Mar;37(3):315-23

Authors: Qiao W, Yang Y, Sebra R, Mendiratta G, Gaedigk A, Desnick RJ, Scott SA

Abstract
The cytochrome P450-2D6 (CYP2D6) enzyme metabolizes ∼25% of common medications, yet homologous pseudogenes and copy number variants (CNVs) make interrogating the polymorphic CYP2D6 gene with short-read sequencing challenging. Therefore, we developed a novel long-read, full gene CYP2D6 single molecule real-time (SMRT) sequencing method using the Pacific Biosciences platform. Long-range PCR and CYP2D6 SMRT sequencing of 10 previously genotyped controls identified expected star (*) alleles, but also enabled suballele resolution, diplotype refinement, and discovery of novel alleles. Coupled with an optimized variant-calling pipeline, CYP2D6 SMRT sequencing was highly reproducible as triplicate intra- and inter-run nonreference genotype results were completely concordant. Importantly, targeted SMRT sequencing of upstream and downstream CYP2D6 gene copies characterized the duplicated allele in 15 control samples with CYP2D6 CNVs. The utility of CYP2D6 SMRT sequencing was further underscored by identifying the diplotypes of 14 samples with discordant or unclear CYP2D6 configurations from previous targeted genotyping, which again included suballele resolution, duplicated allele characterization, and discovery of a novel allele and tandem arrangement. Taken together, long-read CYP2D6 SMRT sequencing is an innovative, reproducible, and validated method for full-gene characterization, duplication allele-specific analysis, and novel allele discovery, which will likely improve CYP2D6 metabolizer phenotype prediction for both research and clinical testing applications.

PMID: 26602992 [PubMed - indexed for MEDLINE]

Cardiovascular pharmacogenomics: current status and future directions.

J Hum Genet. 2016 Jan;61(1):79-85

Authors: Roden DM

Abstract
Drugs are widely used and highly effective in the treatment of heart disease. Nevertheless, in some instances, even drugs effective in a population display lack of efficacy or adverse drug reactions in individual patients, often in an apparently unpredictable fashion. This review summarizes the genomic factors now known to influence variability in responses to widely used cardiovascular drugs such as clopidogrel, warfarin, heparin and statins. Genomic approaches being used to discover new pathways in common cardiovascular diseases and thus potential new targets for drug development are described. Finally, the way in which this new information is likely to be used in an electronic medical record environment is discussed.

PMID: 26178435 [PubMed - indexed for MEDLINE]

Cysteinyl Leukotrienes Pathway Genes, Atopic Asthma and Drug Response: From Population Isolates to Large Genome-Wide Association Studies.

Front Pharmacol. 2016;7:299

Authors: Thompson MD, Capra V, Clunes MT, Rovati GE, Stankova J, Maj MC, Duffy DL

Abstract
Genetic variants associated with asthma pathogenesis and altered response to drug therapy are discussed. Many studies implicate polymorphisms in genes encoding the enzymes responsible for leukotriene synthesis and intracellular signaling through activation of seven transmembrane domain receptors, such as the cysteinyl leukotriene 1 (CYSLTR1) and 2 (CYSLTR2) receptors. The leukotrienes are polyunsaturated lipoxygenated eicosatetraenoic acids that exhibit a wide range of pharmacological and physiological actions. Of the three enzymes involved in the formation of the leukotrienes, arachidonate 5 lipoxygenase 5 (ALOX5), leukotriene C4 synthase (LTC4S), and leukotriene hydrolase (LTA4H) are all polymorphic. These polymorphisms often result in variable production of the CysLTs (LTC4, LTD4, and LTE4) and LTB4. Variable number tandem repeat sequences located in the Sp1-binding motif within the promotor region of the ALOX5 gene are associated with leukotriene burden and bronchoconstriction independent of asthma risk. A 444A > C SNP polymorphism in the LTC4S gene, encoding an enzyme required for the formation of a glutathione adduct at the C-6 position of the arachidonic acid backbone, is associated with severe asthma and altered response to the CYSLTR1 receptor antagonist zafirlukast. Genetic variability in the CysLT pathway may contribute additively or synergistically to altered drug responses. The 601 A > G variant of the CYSLTR2 gene, encoding the Met201Val CYSLTR2 receptor variant, is associated with atopic asthma in the general European population, where it is present at a frequency of ∼2.6%. The variant was originally found in the founder population of Tristan da Cunha, a remote island in the South Atlantic, in which the prevalence of atopy is approximately 45% and the prevalence of asthma is 36%. In vitro work showed that the atopy-associated Met201Val variant was inactivating with respect to ligand binding, Ca(2+) flux and inositol phosphate generation. In addition, the CYSLTR1 gene, located at Xq13-21.1, has been associated with atopic asthma. The activating Gly300Ser CYSLTR1 variant is discussed. In addition to genetic loci, risk for asthma may be influenced by environmental factors such as smoking. The contribution of CysLT pathway gene sequence variants to atopic asthma is discussed in the context of other genes and environmental influences known to influence asthma.

PMID: 27990118 [PubMed - in process]

Incorporating Pharmacogenomics into Health Information Technology, Electronic Health Record and Decision Support System: An Overview.

J Med Syst. 2017 Feb;41(2):19

Authors: Alanazi A

Abstract
As the adoption of information technology in healthcare is rising, the potentiality of moving Pharmacogenomics from benchside to bedside is aggravated. This paper reviews the current status of Pharmacogenomics (PGx) information and the attempts for incorporating them into the Electronic Health Record (EHR) system through Decision Support Systems (DSSs). Rigorous review strategies of PGx information and providing context-relevant recommendations in form of action plan- dose adjustment, lab tests rather than just information- would be ideal for making clinical recommendations out of PGx information. Lastly, realistic projections of what pharmacogenomics can provide is another important aspect in incorporating Pharmacogenomics into health information technology.

PMID: 27987157 [PubMed - in process]

Patient perceptions of care as influenced by a large institutional pharmacogenomic implementation program.

Clin Pharmacol Ther. 2016 Dec 16;:

Authors: McKillip RP, Borden BA, Galecki P, Ham SA, Patrick-Miller L, Hall JP, Hussain S, Danahey K, Siegler M, Sorrentino MJ, Sacro Y, Davis AM, Rubin DT, Lipstreuer K, Polonsky TS, Nanda R, Harper WR, Koyner JL, Burnet DL, Stadler WM, Ratain MJ, Meltzer DO, O'Donnell PH

Abstract
Despite growing clinical use of genomic information, patient perceptions of genomic-based care are poorly understood. We prospectively studied patient-physician pairs who participated in an institutional pharmacogenomic implementation program. Trust/Privacy/Empathy/Medical Decision-Making (MDM)/Personalized Care (PC) dimensions were assessed through patient surveys after clinic visits at which physicians had access to preemptive pharmacogenomic results (Likert scale, 1-minimum/5-maximum; mean [SD]). From 2012-2015, 1,261 surveys were issued to 507 patients, with 792 (62.8%) returned. Privacy, Empathy, MDM and PC scores were significantly higher following visits when physicians considered pharmacogenomic results. Importantly, PC scores were significantly higher after physicians used pharmacogenomic information to guide medication changes (4.0[1.4] vs. 3.0[1.6], P<0.001) compared to prescribing visits without genomic guidance. Multivariable modeling controlling for clinical factors confirmed PC scores were more favorable following visits with genomic-influenced prescribing (OR=3.26 [1.31-8.14], P<0.05). Physicians appear to individualize care when utilizing pharmacogenomic results and this decision-making augmentation is perceived positively by patients. This article is protected by copyright. All rights reserved.

PMID: 27981566 [PubMed - as supplied by publisher]

Pharmacogenomics in the age of personalized medicine.

Drug Discov Today Technol. 2016 Sep - Dec;21-22:11-16

Authors: Dickmann LJ, Ware JA

Abstract
The aim of personalized medicine is to offer the right treatment to the right person at the right dose, thus maximizing efficacy and minimizing toxicity for each individual patient. Pharmacogenomic approaches attempt to refine the aim of personalized medicine by utilizing an individual's germline and somatic DNA signatures to guide treatment. In this review, we highlight the current use of pharmacogenomic based biomarker information in drug labeling. We also present several case studies on the implementation of pharmacogenomic strategies in drug discovery and development. Lastly, we comment on current challenges to implementing pharmacogenomic based testing in the clinic.

PMID: 27978982 [PubMed - in process]

Functional characterization of 34 CYP2A6 allelic variants by assessment of nicotine C-oxidation and coumarin 7-hydroxylation activities.

Drug Metab Dispos. 2016 Dec 14;:

Authors: Hosono H, Kumondai M, Maekawa M, Yamaguchi H, Mano N, Oda A, Hirasawa N, Hiratsuka M

Abstract
Cytochrome P450 2A6 (CYP2A6) is one of the enzymes responsible for the metabolism of therapeutic drugs and tobacco components, such as nicotine, 4-methylnitrosoamino-1-(3-pyridyl)-1-butanone, and N-nitrosodiethylamine. Genetic polymorphisms in CYP2A6 are associated with individual variation in smoking behavior, drug toxicity, and the risk of developing several cancers. In this study, we conducted an in vitro analysis of 34 allelic variants of CYP2A6 using nicotine and coumarin as representative CYP2A6 substrates. These variant CYP2A6 proteins were heterologously expressed in 293FT cells, and their enzymatic activities were assessed based on nicotine C-oxidation and coumarin 7-hydroxylation activities. Among the 34 CYP2A6 variants, CYP2A6.2, CYP2A6.5, CYP2A6.6, CYP2A6.10, CYP2A6.26, CYP2A6.36, and CYP2A6.37 exhibited no enzymatic activity, while 14 other variants exhibited markedly reduced activity toward both nicotine and coumarin. These comprehensive in vitro findings may provide useful insight into individual differences in smoking behavior, drug efficacy, and cancer susceptibility.

PMID: 27974382 [PubMed - as supplied by publisher]

Genetic polymorphisms of pharmacogenomic VIP variants in Li nationality of southern China.

Environ Toxicol Pharmacol. 2016 Mar;42:237-42

Authors: Ding Y, He P, He N, Li Q, Sun J, Yao J, Yi S, Xu H, Wu D, Wang X, Jin T

Abstract
OBJECTIVES: The present study aimed to screen members of the Li nationality in southern China for genotype frequencies of VIP variants and to determine differences between the Li ethnicity and global human population samples in HapMap.
METHODS: In this study, we genotyped 77 very important pharmacogenetic (VIP) variants selected from the pharmacogenomics knowledge base (PharmGKB) in members of the Li population and compared our data with other eleven populations from the HapMap data set.
RESULTS: Our results showed that VDR rs1540339, VKORC1 rs9934438, and MTHFR rs1801133 were most different in Li compared with most of the eleven populations from the HapMap data set. Furthermore, population structure and F-statistics (Fst) analysis also showed differences between the Li and other HapMap populations, and the results suggest that the Li are most genetically similar to the CHD population, and the least similar to the YRI in HapMap.
CONCLUSIONS: The findings of our study complement the pharmacogenomics database with information on members of the Li ethnicity and provide a stronger scientific basis for safer drug administration, which may help clinicians to predict individual drug responses, thereby avoiding the risk of adverse effects and optimizing efficacy in this population.

PMID: 26901752 [PubMed - indexed for MEDLINE]

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

Pharmacogenomics[Title/Abstract] AND ("2005/01/01"[PDAT] : "3000"[PDAT])

These pubmed results were generated on 2016/12/15

PubMed comprises more than 24 million 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.