A balancing act in cardiac hypertrophy.

Cardiovasc Res. 2016 07 01;111(1):8-9

Authors: Matkovich SJ

PMID: 27216864 [PubMed - indexed for MEDLINE]

12 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 2017/07/19

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.

Genetic Contribution to Alcohol Dependence: Investigation of a Heterogeneous German Sample of Individuals with Alcohol Dependence, Chronic Alcoholic Pancreatitis, and Alcohol-Related Cirrhosis.

Genes (Basel). 2017 Jul 17;8(7):

Authors: Treutlein J, Frank J, Streit F, Reinbold CS, Juraeva D, Degenhardt F, Rietschel L, Witt SH, Forstner AJ, Ridinger M, Strohmaier J, Wodarz N, Dukal H, Foo JC, Hoffmann P, Herms S, Heilmann-Heimbach S, Soyka M, Maier W, Gaebel W, Dahmen N, Scherbaum N, Müller-Myhsok B, Lucae S, Ising M, Stickel F, Berg T, Roggenbuck U, Jöckel KH, Scholz H, Zimmermann US, Buch S, Sommer WH, Spanagel R, Brors B, Cichon S, Mann K, Kiefer F, Hampe J, Rosendahl J, Nöthen MM, Rietschel M

Abstract
The present study investigated the genetic contribution to alcohol dependence (AD) using genome-wide association data from three German samples. These comprised patients with: (i) AD; (ii) chronic alcoholic pancreatitis (ACP); and (iii) alcohol-related liver cirrhosis (ALC). Single marker, gene-based, and pathway analyses were conducted. A significant association was detected for the ADH1B locus in a gene-based approach (puncorrected = 1.2 × 10(-6); pcorrected = 0.020). This was driven by the AD subsample. No association with ADH1B was found in the combined ACP + ALC sample. On first inspection, this seems surprising, since ADH1B is a robustly replicated risk gene for AD and may therefore be expected to be associated also with subgroups of AD patients. The negative finding in the ACP + ALC sample, however, may reflect genetic stratification as well as random fluctuation of allele frequencies in the cases and controls, demonstrating the importance of large samples in which the phenotype is well assessed.

PMID: 28714907 [PubMed]

Differential Analysis of Genetic, Epigenetic, and Cytogenetic Abnormalities in AML.

Int J Genomics. 2017;2017:2913648

Authors: Islam M, Mohamed Z, Assenov Y

Abstract
Acute myeloid leukemia (AML) is a haematological malignancy characterized by the excessive proliferation of immature myeloid cells coupled with impaired differentiation. Many AML cases have been reported without any known cytogenetic abnormalities and carry no mutation in known AML-associated driver genes. In this study, 200 AML cases were selected from a publicly available cohort and differentially analyzed for genetic, epigenetic, and cytogenetic abnormalities. Three genes (FLT3, DNMT3A, and NPMc) are found to be predominantly mutated. We identified several aberrations to be associated with genome-wide methylation changes. These include Del (5q), T (15; 17), and NPMc mutations. Four aberrations-Del (5q), T (15; 17), T (9; 22), and T (9; 11)-are significantly associated with patient survival. Del (5q)-positive patients have an average survival of less than 1 year, whereas T (15; 17)-positive patients have a significantly better prognosis. Combining the methylation and mutation data reveals three distinct patient groups and four clusters of genes. We speculate that combined signatures have the better potential to be used for subclassification of AML, complementing cytogenetic signatures. A larger sample cohort and further investigation of the effects observed in this study are required to enable the clinical application of our patient classification aided by DNA methylation.

PMID: 28713819 [PubMed]

Predictive biomarkers of immunotherapy for non-small cell lung cancer: results from an Experts Panel Meeting of the Italian Association of Thoracic Oncology.

Transl Lung Cancer Res. 2017 Jun;6(3):373-386

Authors: Gridelli C, Ardizzoni A, Barberis M, Cappuzzo F, Casaluce F, Danesi R, Troncone G, De Marinis F

Abstract
Unleashing the potential of immune system to fight cancer has become one of the main promising treatment modalities for advanced non-small cell lung cancer (NSCLC). The knowledge of numerous factors that come into play in the cancer-immunity cycle provide a wide range of potential therapeutic targets, including monoclonal antibodies that inhibits the programmed death-1 (PD-1) checkpoint pathway. Over the last two years, nivolumab, pembrolizumab and atezolizumab received approval for treatment of pretreated advanced NSCLC, and more recently, immunotherapy with pembrolizumab is the new standard of care as first-line in patients with high levels of programmed death-ligand 1 (PD-L1) expression. Selection of patients is mandatory and PD-L1 is the only biomarker currently available in clinical practice. However, PD-L1 staining is an imperfect marker, whose negativity does not exclude a response to immunotherapy, as well as the roughly half of patients are "not-responders" despite high tumor PD-L1 levels. The right cut-off, the differences among various immune checkpoint inhibitors and among various antibody clones, and a not trivial activity reported even in PD-L1 negative tumors are questions still open. New biomarkers beyond to PD-L1 assays as well as new strategies, including combination of immune checkpoint inhibitors are under investigation.

PMID: 28713682 [PubMed]

Comparative genomic and phylogenetic analysis of a toxigenic clinical isolate of Corynebacterium diphtheriae strain B-D-16-78 from Malaysia.

Infect Genet Evol. 2017 Jul 12;:

Authors: Hong KW, Asmah Hani AW, Nurul Aina Murni CA, Pusparani RR, Chong CK, Verasahib K, Yusoff WNW, Noordin NM, Tee KK, Yin WF, Yu CY, Ang GY, Chan KG

Abstract
In this study, we report the comparative genomics and phylogenetic analysis of Corynebacterium diphtheriae strain B-D-16-78 that was isolated from a clinical specimen in 2016. The complete genome of C. diphtheriae strain B-D-16-78 was sequenced using PacBio Single Molecule, Real-Time sequencing technology and consists of a 2,474,151-bp circular chromosome with an average GC content of 53.56%. The core genome of C. diphtheriae was also deduced from a total of 74 strains with complete or draft genome sequences and the core genome-based phylogenetic analysis revealed close genetic relationship among strains that shared the same MLST allelic profile. In the context of CRISPR-Cas system, which confers adaptive immunity against re-invading DNA, 73 out of 86 spacer sequences were found to be unique to Malaysian strains which harboured only type-II-C and/or type-I-E-a systems. A total of 48 tox genes which code for the diphtheria toxin were retrieved from the 74 genomes and with the exception of one truncated gene, only nucleotide substitutions were detected when compared to the tox gene sequence of PW8. More than half were synonymous substitution and only two were nonsynonymous substitutions whereby H24Y was predicted to have a damaging effect on the protein function whilst T262V was predicted to be tolerated. Both toxigenic and non-toxigenic toxin-gene bearing strains have been isolated in Malaysia but the repeated isolation of toxigenic strains with the same MLST profile suggests the possibility of some of these strains may be circulating in the population. Hence, efforts to increase herd immunity should be continued and supported by an effective monitoring and surveillance system to track, manage and control outbreak of cases.

PMID: 28711373 [PubMed - as supplied by publisher]

Genetics of Juvenile Idiopathic Arthritis.

Rheum Dis Clin North Am. 2017 Aug;43(3):435-448

Authors: Hersh AO, Prahalad S

Abstract
Juvenile idiopathic arthritis (JIA) affects approximately 1 in 1000 US children. The cause of JIA is most likely multifactorial and due to an interplay of genetics and environmental factors. This article summarizes the known genetic risk factors for JIA that have been identified, and in some cases replicated, using a variety of methods, including genomewide association and candidate gene association studies. A brief discussion regarding pharmacogenomics and studies to data linking genetics to treatment response and outcomes is included.

PMID: 28711144 [PubMed - in process]

Precision Medicine in Rheumatoid Arthritis.

Rheum Dis Clin North Am. 2017 Aug;43(3):377-387

Authors: Bluett J, Barton A

Abstract
Treatment of rheumatoid arthritis (RA) has substantially improved in recent years because of the development of novel drugs. However, response is not universal for any of the treatment options, and selection of an effective therapy is currently based on a trial-and-error approach. Delayed treatment response increases the risk of progressive joint damage and resultant disability and also has a significant impact on quality of life for patients. For many drugs, the patient's genetic background influences response to therapy, and understanding the genetics of response to therapy in RA may allow for targeted personalized health care.

PMID: 28711140 [PubMed - in process]

Genotypic diversity and phenotypic traits of Streptococcus mutans isolates and their relation to severity of early childhood caries.

BMC Oral Health. 2017 Jul 14;17(1):115

Authors: Valdez RMA, Duque C, Caiaffa KS, Dos Santos VR, Loesch MLA, Colombo NH, Arthur RA, Negrini TC, Boriollo MFG, Delbem ACB

Abstract
BACKGROUND: Early childhood caries (ECC) is an aggressive condition that can affect teeth of young children. This study aimed to evaluate genotypic diversity and phenotypic traits of S. mutans isolated from dental biofilms of children with different caries status in comparison with caries free (CF) children.
METHODS: Streptococcus mutans strains were isolated from supragingival biofilm samples of CF, ECC and severe-ECC (S-ECC) children and genotyped by arbitrary-primer polymerase chain reaction - AP-PCR. S. mutans genotypes were tested for their ability to reduce the suspension pH through glycolysis, to tolerate extreme acid challenge and by their ability to form biofilm. Response variables were analyzed by ANOVA/Tukey or Kruskal-Wallis/Mann-Whitney tests at a 5% of significance.
RESULTS: There was an increase in the prevalence of Streptococcus mutans in biofilms with the severity of dental caries. No differences in genotypic diversity and in acidogenicity of genotypes were found among CF, ECC and S-ECC children. S mutans strains with genotypes more characteristic for ECC and S-ECC children formed more biofilms than those identified in CF children. The strains isolated from S-ECC children were highly acid tolerant.
CONCLUSION: Although S. mutans genotypic diversity was similar among the groups of children, phenotypic traits of S. mutans, especially the acid tolerance response, could explain the severity of early childhood caries.

PMID: 28709424 [PubMed - in process]

Can Psychological, Social and Demographical Factors Predict Clinical Characteristics Symptomatology of Bipolar Affective Disorder and Schizophrenia?

Psychiatr Q. 2016 Sep;87(3):501-13

Authors: Maciukiewicz M, Pawlak J, Kapelski P, Łabędzka M, Skibinska M, Zaremba D, Leszczynska-Rodziewicz A, Dmitrzak-Weglarz M, Hauser J

Abstract
Schizophrenia (SCH) is a complex, psychiatric disorder affecting 1 % of population. Its clinical phenotype is heterogeneous with delusions, hallucinations, depression, disorganized behaviour and negative symptoms. Bipolar affective disorder (BD) refers to periodic changes in mood and activity from depression to mania. It affects 0.5-1.5 % of population. Two types of disorder (type I and type II) are distinguished by severity of mania episodes. In our analysis, we aimed to check if clinical and demographical characteristics of the sample are predictors of symptom dimensions occurrence in BD and SCH cases. We included total sample of 443 bipolar and 439 schizophrenia patients. Diagnosis was based on DSM-IV criteria using Structured Clinical Interview for DSM-IV. We applied regression models to analyse associations between clinical and demographical traits from OPCRIT and symptom dimensions. We used previously computed dimensions of schizophrenia and bipolar affective disorder as quantitative traits for regression models. Male gender seemed protective factor for depression dimension in schizophrenia and bipolar disorder sample. Presence of definite psychosocial stressor prior disease seemed risk factor for depressive and suicidal domain in BD and SCH. OPCRIT items describing premorbid functioning seemed related with depression, positive and disorganised dimensions in schizophrenia and psychotic in BD. We proved clinical and demographical characteristics of the sample are predictors of symptom dimensions of schizophrenia and bipolar disorder. We also saw relation between clinical dimensions and course of disorder and impairment during disorder.

PMID: 26646576 [PubMed - indexed for MEDLINE]

12 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 2017/07/14

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.

Payer coverage policies for multigene tests.

Nat Biotechnol. 2017 Jul 12;35(7):614-617

Authors: Phillips KA, Deverka PA, Trosman JR, Douglas MP, Chambers JD, Weldon CB, Dervan AP

PMID: 28700544 [PubMed - in process]

Personalizing antiplatelet prescribing using genetics for patients undergoing percutaneous coronary intervention.

Expert Rev Cardiovasc Ther. 2017 Jul 12;:

Authors: Cavallari LH

Abstract
INTRODUCTION: Clopidogrel is commonly prescribed with aspirin to reduce the risk for adverse cardiovascular events after percutaneous coronary intervention (PCI). However, there is significant inter-patient variability in clopidogrel response. The CYP2C19 enzyme is involved in the biotransformation of clopidogrel to its pharmacologically active form, and variation in the CYP2C19 gene contributes to clopidogrel response variability. Areas covered. This article describes the impact of CYP2C19 genotype on clopidogrel pharmacokinetics, pharmacodynamics, and effectiveness. Examples of clinical implementation of CYP2C19 genotyping-guided antiplatelet therapy for patients undergoing PCI are also described as are emerging outcomes data with this treatment approach. Expert commentary. A large clinical trial evaluating outcomes with CYP2C19 genotype-guided antiplatelet therapy after PCI is on-going. In the meantime, data from pragmatic and observational studies and smaller trials support improved outcomes with genotyping after PCI and use of alternative antiplatelet therapy in patients with a CYP2C19 genotype associated with reduced clopidogrel effectiveness.

PMID: 28699807 [PubMed - as supplied by publisher]

Pharmacogenomics Implementation: Considerations for Selecting a Reference Laboratory.

Pharmacotherapy. 2017 Jul 12;:

Authors: Vo TT, Bell GC, Owusu Obeng A, Hicks JK, Dunnenberger HM

Abstract
One of the initial steps for implementing pharmacogenomics into routine patient care is selecting an appropriate clinical laboratory to perform the testing. With the rapid advances in genotyping technologies, many clinical laboratories are now performing pharmacogenomic testing. Selection of a reference laboratory depends on whether a particular genotype assay is already performed by an internal healthcare organization laboratory or only available externally. Other factors for consideration are coverage of genomic variants important for your patient population, technical support, and cost. In some instances, the decision to select a particular reference laboratory may be the responsibility of the clinician who is recommending genomic interrogation. There is limited guidance describing the laboratory characteristics to consider when selecting a reference laboratory. We provide practical considerations for selecting a clinical laboratory for pharmacogenomic testing broadly categorized into 4 domains: (1) pharmacogene and variant selection, (2) logistics, (3) reporting of results, and (4) test costs along with reimbursement. This article is protected by copyright. All rights reserved.

PMID: 28699700 [PubMed - as supplied by publisher]

Review of Opioid Pharmacogenetics and Considerations for Pain Management.

Pharmacotherapy. 2017 Jul 12;:

Authors: Owusu Obeng A, Hamadeh I, Smith M

Abstract
Opioid analgesics are the standards of care for the treatment of moderate to severe nociceptive pain, particularly in the setting of cancer and surgery. Their analgesic properties mainly emanate from stimulation of the μ receptors, which are encoded by the OPRM1 gene. Hepatic metabolism represents the major route of elimination, which, for some opioids, namely codeine and tramadol, is necessary for their bioactivation into more potent analgesics. The highly polymorphic nature of the genes coding for phase I and phase II enzymes (pharmacokinetics genes) that are involved in the metabolism and bioactivation of opioids suggests a potential interindividual variation in their disposition and, most likely, response. In fact, such an association has been substantiated in several pharmacokinetic studies described in this review, in which drug exposure and/or metabolism differed significantly based on the presence of polymorphisms in these pharmacokinetics genes. Furthermore, in some studies, the observed variability in drug exposure translated into differences in the incidence of opioid-related adverse effects, particularly nausea, vomiting, constipation, and respiratory depression. Although the influence of polymorphisms in pharmacokinetics genes, as well as pharmacodynamics genes (OPRM1 and COMT) on response to opioids has been a subject of intense research, the results have been somehow conflicting, with some evidence insinuating for a potential role for OPRM1. The Clinical Pharmacogenetics Implementation Consortium guidelines provide CYP2D6-guided therapeutic recommendations to individualize treatment with tramadol and codeine. However, implementation guidelines for other opioids, which are more commonly used in real-world settings for pain management, are currently lacking. Hence, further studies are warranted to bridge this gap in our knowledge base and ultimately ascertain the role of pharmacogenetic markers as predictors of response to opioid analgesics. This article is protected by copyright. All rights reserved.

PMID: 28699646 [PubMed - as supplied by publisher]

Pharmacogenetics and Pharmacogenomics of Targeted Therapeutics in Chronic Myeloid Leukemia.

Mol Diagn Ther. 2017 Jul 11;:

Authors: Nath A, Wang J, Stephanie Huang R

Abstract
The advent of targeted therapeutics has greatly improved outcomes of chronic myeloid leukemia (CML) patients. Despite increased efficacy and better clinical responses over cytotoxic chemotherapies, many patients receiving targeted drugs exhibit a poor initial response, develop drug resistance, or undergo relapse after initial success. This inter-individual variation in response has heightened the interest in studying pharmacogenetics and pharmacogenomics (PGx) of cancer drugs. In this review, we discuss the influence of various germline and somatic factors on targeted drug response in CML. Specifically, we examine the role of genetic variants in drug metabolism genes, i.e. CYP3A family genes, and drug transporters, i.e. ABC and SLC family genes. Additionally, we focus on acquired somatic variations in BCR-ABL1, and the potential role played by additional downstream signaling pathways, in conferring resistance to targeted drugs in CML. This review highlights the importance of PGx of targeted therapeutics and its potential application to improving treatment decisions and patient outcomes.

PMID: 28698977 [PubMed - as supplied by publisher]

Bacterial Community Profile of the Gut Microbiota Differs between Hypercholesterolemic Subjects and Controls.

Biomed Res Int. 2017;2017:8127814

Authors: Rebolledo C, Cuevas A, Zambrano T, Acuña JJ, Jorquera MA, Saavedra K, Martínez C, Lanas F, Serón P, Salazar LA, Saavedra N

Abstract
The role of gut microbiota in the development of metabolic illnesses has been abundantly demonstrated. Recent studies suggest that gut microbiota alterations may also be related to the development of hypercholesterolemia. Therefore, we aimed to assess differences in the gut bacterial community profiles between hypercholesterolemic subjects and controls. Thirty cases diagnosed with hypercholesterolemia and 27 normocholesterolemic controls were included. A fasting whole blood sample was obtained to determine the lipid profile. In parallel, stool samples were collected and total DNA was isolated to assess the bacterial community profiles by denaturing gradient gel electrophoresis (DGGE). In addition, the Richness, Shannon-Weaver, and Simpson indexes were used to evaluate the richness and diversity of bacterial communities. As expected, serum concentrations of total cholesterol, triglycerides, and LDL-cholesterol were significantly higher in the cases compared with controls. Moreover, DGGE analysis showed a lower richness and diversity of bacterial communities in hypercholesterolemic subjects. In conclusion, our results showed differences in the profiles of bacterial communities between hypercholesterolemic subjects and controls, suggesting a possible role of the gut microbiota in the development of hypercholesterolemia.

PMID: 28698878 [PubMed - in process]

Gene-gene and gene-environment interactions influence platinum-based chemotherapy response and toxicity in non-small cell lung cancer patients.

Sci Rep. 2017 Jul 11;7(1):5082

Authors: Cui JJ, Wang LY, Zhu T, Gong WJ, Zhou HH, Liu ZQ, Yin JY

Abstract
Platinum-based chemotherapy is a major therapeutic regimen of lung cancer. Various single nucleotide polymorphisms (SNPs) reported were associated with platinum-based chemotherapy response and drug toxicity. However, neither of the studies explored this association from SNP-SNP interaction perspective nor taking into effects of SNP-environment consideration simultaneously. We genotyped 504 polymorphisms and explore the association of gene-gene and gene-environment interactions with platinum-based chemotherapy response and toxicity in 490 NSCLC patients. 16 SNPs were found significantly associated with platinum-based chemotherapy, and they were picked out as study object in the validation cohort. We recruited 788 patients in the validation cohort. We found that HSPD1 rs17730989-SUMF1 rs2633851 interaction was associated with platinum-based chemotherapy-induced hematologic toxicity (adjusted OR = 0.233, P = 0.018). In addition, the combined effect of ABCG2 rs2231142-CES5A rs3859104 was significantly associated with overall toxicity (adjusted OR = 8.044, P = 4.350 × 10(-5)). Besides, the model of ARHGAP26 rs3776332-ERCC6 rs2228528-SLC2A1 rs4658-histology was associated with platinum-based chemotherapeutic response. Gene-gene and gene-environment interactions have been identified to contribute to chemotherapy sensitivity and toxicity. They can potentially predict drug response and toxicity of platinum-based chemotherapy in NSCLC patients.

PMID: 28698656 [PubMed - in process]

V-J combinations of T-cell receptor predict responses to erythropoietin in end-stage renal disease patients.

J Biomed Sci. 2017 Jul 11;24(1):43

Authors: Wong HS, Chang CM, Kao CC, Hsu YW, Liu X, Chang WC, Wu MS, Chang WC

Abstract
BACKGROUND: Anemia is common among end-stage renal disease (ESRD) patients who undergone hemodialysis. The total reduction of red blood cell (RBC) count is associated with poor prognosis in these patients. Although erythropoietin (EPO) has been used as an effective treatment for ESRD patients with anemia, a large number of patients still present poor responses to EPO treatment.
METHODS: We measured T-cell receptor sequencing profiles, including length of complementarity-deteremining region 3 (CDR3), intra- and inter-group (EPO resistant vs. responsive) clonotype diversity, V(D)J usage profiles and V-J combinations from ESRD patients and to investigate the correlation between these features and EPO treatment efficacy.
RESULTS: Our results revealed statistical significance in the top 3 ~ 15 most abundant joint distributions of Vβ/Jβ among the two groups, suggesting the importance of V or J gene utilization in the EPO response of ESRD patients.
CONCLUSIONS: In summary, we provided evidence addressing the potential correlation between the immune repertoire and EPO response in ESRD patients.
TRIAL REGISTRATION: TMU-JIRB 201309026. Registered 16 October 2013.

PMID: 28697735 [PubMed - in process]

15 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 2017/07/12

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.