Abstract:
:Asthma is one of the most common respiratory diseases, where inhalation and exhalation are obstructed due to narrowing of the airways by broncho-constriction or by inflammation. Among all the available anti-asthma therapies, beta2-agonists are the most effective bronchodilators available, and give rapid relief of asthma symptoms. Evidence suggests that the degree of beta2-agonist response varies greatly between patients and genetic factors have a major role in it. Despite several studies on the beta2-agonist pharmacogenetics, significant gaps in knowledge still remain and need to be resolved before the pharmacotyping of beta2-agonist responsiveness comes to clinical practice. As we know, beta2-agonists show their influence by targeting beta2-adrenergic receptors, leading to the activation of beta2-adrenergic receptors and its downstream cascade. Signaling through beta2-adrenergic receptors mediates numerous airway functions by regulating broncho-constriction and dilation pathways. Therefore, it is an important prerequisite to understand these pathways, which will assist in defining the variability in therapeutic responses for beta2-agonists. Owing to the complexity of the action of a beta2-agonist and its therapeutic response, a broader genomics approach will help in optimizing therapy for the individual patient. This might be achieved by considering and focusing on receptor/s at which the drug binds directly, signal transduction cascades or downstream proteins and proteins involved in the relaxation and constriction of the airway smooth muscle. Considering that a drug response may involve a large number of proteins, it seems unlikely that a single polymorphism or haplotype in a single gene would explain a high degree of drug response variability in a consistent fashion. Thus, it shows that a polygenic approach will be more appropriate. In order to follow this, the mode of action of the beta2-agonist and its downstream signaling cascade should essentially be assessed to resolve the beta2-agonist enigma.
journal_name
Pharmacogenomicsjournal_title
Pharmacogenomicsauthors
Bhatnagar P,Guleria R,Kukreti Rdoi
10.2217/14622416.7.6.919subject
Has Abstractpub_date
2006-09-01 00:00:00pages
919-33issue
6eissn
1462-2416issn
1744-8042journal_volume
7pub_type
杂志文章,评审相关文献
PHARMACOGENOMICS文献大全abstract::The second Annual Meeting of the UK Pharmacogenetics and Stratified Medicine Network was held on 28 September 2011 at The Wellcome Trust Conference Centre on the Wellcome Trust Genome Campus at Hinxton, Cambridge, UK. The meeting preceded the annual Pharmacogenomics and Personalized Medicine conference, which was held...
journal_title:Pharmacogenomics
pub_type:
doi:10.2217/pgs.11.162
更新日期:2012-01-01 00:00:00
abstract::The first observations of inherited differences in drug effects in the 1950s led to the recognition of a genetic basis for drug response. With the development of genetics and molecular biology, it became clear that certain drug responses could be associated with specific genetic variations or polymorphisms. There are ...
journal_title:Pharmacogenomics
pub_type: 杂志文章,评审
doi:10.1517/14622416.3.4.453
更新日期:2002-07-01 00:00:00
abstract::Translational research is frequently used in the bioscience literature to refer to the translation of basic science into practical applications at the point of patient care. With the introduction of theragnostics, a new medical subspecialty that fuses therapeutics and diagnostic medicine with the goal of providing ind...
journal_title:Pharmacogenomics
pub_type: 杂志文章,评审
doi:10.2217/14622416.8.2.177
更新日期:2007-02-01 00:00:00
abstract:AIM:We examined whether HLA-DRB1*1501 and four VDR SNPs influence the macrophage response to infection with Mycobacterium tuberculosis (Mtb) via innate immune versus drug treatment or drug delivery mechanisms. MATERIALS & METHODS:Monocyte-derived macrophages from 24 healthy donors were infected with Mtb in vitro. Surv...
journal_title:Pharmacogenomics
pub_type: 杂志文章
doi:10.2217/pgs.13.12
更新日期:2013-04-01 00:00:00
abstract::DxS is a pharmacogenomics business operating at the interface between genetic diagnostics and the pharmaceutical industry. The company strategy is to enable pharmacogenomics by the provision of genetic analysis services to the healthcare sector. The services provide support for drug discovery, drug development and als...
journal_title:Pharmacogenomics
pub_type: 杂志文章
doi:10.1517/phgs.4.1.97.22580
更新日期:2003-01-01 00:00:00
abstract::Interindividual variability in drug response and the emergence of adverse drug effects are the main causes of treatment failure in cancer therapy. Functional membrane drug transporters play important roles in altering pharmacokinetic profile, resistance to treatment, toxicity and patient survival. Pharmacogenetic stud...
journal_title:Pharmacogenomics
pub_type: 杂志文章,评审
doi:10.2217/pgs.12.165
更新日期:2012-12-01 00:00:00
abstract::Healthcare professionals (e.g., physicians, physician assistants, pharmacists, nurses and genetic counselors) believe pharmacogenomics (PGx) is essential to personalized medicine; however, they still lack confidence prescribing, dosing, interacting with other healthcare professionals and counseling patients with regar...
journal_title:Pharmacogenomics
pub_type: 杂志文章
doi:10.2217/pgs.12.113
更新日期:2012-09-01 00:00:00
abstract::This narrative review describes implementation, current status and perspectives of a pharmacogenomic (PGx) program at the Brazilian National Cancer Institute (INCA), targeting the cancer chemotherapeutic drugs - fluoropyrimidines, irinotecan and thiopurines. This initiative, designed as a research project, was support...
journal_title:Pharmacogenomics
pub_type: 杂志文章
doi:10.2217/pgs-2020-0016
更新日期:2020-06-01 00:00:00
abstract:AIM:The present study explored the integrative effect of genes encoding methadone pharmacokinetic and pharmacodynamic pathways on methadone maintenance doses in Han Chinese Patients. MATERIALS & METHODS:Genomic DNA was extracted from 321 opioid-dependent patients and 202 healthy controls, and realtime-PCR and PCR-RFLP...
journal_title:Pharmacogenomics
pub_type: 杂志文章
doi:10.2217/pgs.11.96
更新日期:2011-11-01 00:00:00
abstract:AIMS:Variant alleles of the CYP2C19 gene were recently associated with survival in breast cancer patients on tamoxifen therapy. CYP2C19 is one of the enzymes involved in the metabolism of tamoxifen into active metabolites. We investigated the hypothesis that CYP2C19*2 and *3 variants, known for their lack of enzyme act...
journal_title:Pharmacogenomics
pub_type: 杂志文章
doi:10.2217/pgs.10.112
更新日期:2010-10-01 00:00:00
abstract::The 4th US FDA/Industry workshop, in a series on Pharmacogenomics, was on 'Biomarkers and Pharmacogenomics in Drug Development and Regulatory Decision Making' and was held on December 10-12, 2007 in Bethesda, MD, USA, with clear objectives to continue the dialogue that began in 2002 for enabling the use of biomarkers ...
journal_title:Pharmacogenomics
pub_type:
doi:10.2217/14622416.10.1.111
更新日期:2009-01-01 00:00:00
abstract:AIM:A population pharmacokinetic (PPK) analysis was conducted to describe the influence of GSTA1 polymorphisms on intravenous busulfan in adults undergoing allogeneic hematopoietic stem cell transplantation. PATIENTS & METHODS:A PPK model was developed from 36 patients by a one-compartment model with first-order elimi...
journal_title:Pharmacogenomics
pub_type: 杂志文章
doi:10.2217/pgs.15.98
更新日期:2015-01-01 00:00:00
abstract:AIM:We conducted a genome-wide association study using the Illumina Exome Array to identify coding SNPs that may explain additional warfarin dose variability. PATIENTS & METHODS:Analysis was performed after adjustment for clinical variables and genetic factors known to influence warfarin dose among 1680 warfarin users...
journal_title:Pharmacogenomics
pub_type: 杂志文章
doi:10.2217/pgs-2017-0046
更新日期:2017-07-01 00:00:00
abstract::ALK was first reported in 1994 as a translocation in anaplastic large cell lymphoma and then described with different abnormalities in a number of tumors. Recently, a shortly accumulated biomedical research clarified the numerous biological processes underlying its ability to support cancer development, growth and pro...
journal_title:Pharmacogenomics
pub_type: 杂志文章
doi:10.2217/pgs-2016-0166
更新日期:2017-02-01 00:00:00
abstract::High-throughput genotyping approaches are being developed to meet the demands of pharmacogenomnics, where numerous individuals are studied with thousands of single nucleotide polymorphism (SNP) markers. All non-gel-based genotyping approaches achieve allelic discrimination by one of four mechanisms: allele-specific hy...
journal_title:Pharmacogenomics
pub_type: 杂志文章,评审
doi:10.1517/14622416.1.1.95
更新日期:2000-02-01 00:00:00
abstract:INTRODUCTION:Most cancer pharmacogenetic studies use germline DNA, as tumor tissue is often inaccessible in the advanced disease setting. However, this relies on the assumption that germline DNA is representative of the tumor genotype. To date, there has been little attention paid to defining the relationship between t...
journal_title:Pharmacogenomics
pub_type: 杂志文章
doi:10.2217/14622416.6.8.873
更新日期:2005-12-01 00:00:00
abstract::For the last 40 years, 5-fluorouracil (5-FU) has remained the treatment of choice in both the adjuvant and advanced treatment of colorectal cancer (CRC). However, 5-FU monotherapy produces response rates of only 10-20% in the advanced setting. 5-FU has been combined with newer agents, such as oxaliplatin and irinoteca...
journal_title:Pharmacogenomics
pub_type: 杂志文章,评审
doi:10.2217/14622416.6.6.603
更新日期:2005-09-01 00:00:00
abstract::The multi-drug resistant transporter MDR1/P-glycoprotein, the gene product of MDR1, is a glycosylated membrane protein of 170 kDa, belonging to the ATP-binding cassette (ABC) superfamily of membrane transporters. MDR1 was originally isolated from resistant tumor cells as part of the mechanism of multi-drug resistance,...
journal_title:Pharmacogenomics
pub_type: 杂志文章,评审
doi:10.1517/phgs.4.4.397.22747
更新日期:2003-07-01 00:00:00
abstract:AIM:To determine the availability of pharmacogenetic and pharmacogenomic information for healthcare professionals in France during 2009 for anticancer drugs. MATERIALS & METHODS:We searched in the informatic version of the VIDAL dictionary which is currently used by healthcare professionals in France. We then compared...
journal_title:Pharmacogenomics
pub_type: 杂志文章,评审
doi:10.2217/pgs.10.178
更新日期:2011-05-01 00:00:00
abstract::Drugs used to treat psychiatric disorders, even when taken as directed, fail to provide adequate relief for a sizeable proportion of patients. Despite our advancements in understanding human genetics and development of high-throughput tools to probe variation, pharmacogenomics has yielded marginal ability to predict d...
journal_title:Pharmacogenomics
pub_type: 杂志文章,评审
doi:10.2217/pgs-2017-0104
更新日期:2017-10-01 00:00:00
abstract:AIM:Genetic variants contribute to statins' therapeutic variability. SREBF-SCAP pathway is a key player in lipid homeostasis. Hence, effect of SREBF-SCAP polymorphisms on therapeutic response was studied. PATIENTS & METHODS:Metabolic syndrome patients of either sex were prescribed rosuvastatin 10 mg for 24 weeks. Clin...
journal_title:Pharmacogenomics
pub_type: 临床试验,杂志文章
doi:10.2217/pgs-2017-0181
更新日期:2018-02-01 00:00:00
abstract:AIMS:The importance of polymorphisms in the dihydropyrimidine dehydrogenase gene (DPYD) for the prediction of severe toxicity in 5-fluorouracil (5-FU)-based chemotherapy is still unclear. This study aims to assess the predictive value of DPYD variation with respect to previously described DPYD variants for 5-FU toxicit...
journal_title:Pharmacogenomics
pub_type: 杂志文章
doi:10.2217/pgs.09.28
更新日期:2009-06-01 00:00:00
abstract:AIM:To determine the clinical and genetic predictors of the dipeptidyl peptidase-4 (DPP-4) inhibitor treatment response in Type 2 diabetes mellitus (T2DM) patients. PATIENTS & METHODS:DPP4, WFS1 and KCNJ11 gene polymorphisms were genotyped in a cohort study of 662 T2DM patients treated with DPP-4 inhibitors sitaglipti...
journal_title:Pharmacogenomics
pub_type: 杂志文章
doi:10.2217/pgs-2016-0010
更新日期:2016-06-01 00:00:00
abstract:AIM:To determine if copy number variants contribute to warfarin dose requirements, we investigated CYP2C9, VKORC1, CYP4F2, GGCX and CALU for deletions and duplications in a multiethnic patient population treated with therapeutic doses of warfarin. PATIENTS & METHODS:DNA samples from 178 patients were subjected to copy...
journal_title:Pharmacogenomics
pub_type: 杂志文章
doi:10.2217/pgs.11.156
更新日期:2012-02-01 00:00:00
abstract::Large differences are observed in chemotherapy response between breast cancer patients, with a substantial part of this variability being explained by genetic factors. Polymorphisms in genes encoding drug-metabolizing enzymes, drug transporters and drug targets influence the pharmacokinetics and pharmacodynamics of th...
journal_title:Pharmacogenomics
pub_type: 杂志文章,评审
doi:10.2217/pgs.12.44
更新日期:2012-04-01 00:00:00
abstract::Cancers of the colon are commonly treated with fluoropyrimidines, which often cause severe toxicities in patients with certain variants in DPYD. Y186C (rs115232898) and a variant in the 3' untranslated region (rs12132152) are uncommon alleles previously observed in African-Americans. An African-American female underwe...
journal_title:Pharmacogenomics
pub_type: 杂志文章
doi:10.2217/pgs-2020-0120
更新日期:2021-01-01 00:00:00
abstract::Fibromyalgia syndrome (FMS) is a common chronic widespread pain syndrome mainly affecting women. Although the etiology of FMS is not completely understood, varieties of neuroendocrine disturbances, as well as abnormalities of autonomic function, have been implicated in its pathogenesis. The exposure of a genetically p...
journal_title:Pharmacogenomics
pub_type: 杂志文章,评审
doi:10.2217/14622416.8.1.67
更新日期:2007-01-01 00:00:00
abstract::Aim: To determine if selected serotonergic and noradrenergic gene variants are associated with heroin addiction. Subjects & methods: A total of 126 variants in 19 genes in subjects with Dutch European ancestry from The Netherlands. Subjects included 281 opioid-dependent volunteers in methadone maintenance or heroin-as...
journal_title:Pharmacogenomics
pub_type: 杂志文章
doi:10.2217/pgs-2018-0137
更新日期:2019-04-01 00:00:00
abstract::Quantitative trait analysis (QTA) can be used to test whether the expression of a particular gene significantly correlates with some ordinal variable. To limit the number of false discoveries in the gene list, a multivariate permutation test can also be performed. The purpose of this study is to identify peripheral bl...
journal_title:Pharmacogenomics
pub_type: 杂志文章
doi:10.2217/14622416.7.3.395
更新日期:2006-04-01 00:00:00
abstract:BACKGROUND:Essential hypertension arises from the combined effect of genetic and environmental factors. A pharmacogenomics approach could help to identify additional molecular mechanisms involved in its pathogenesis. AIM:The aim of SOPHIA study was to identify genetic polymorphisms regulating blood pressure response t...
journal_title:Pharmacogenomics
pub_type: 杂志文章
doi:10.2217/pgs.14.119
更新日期:2014-09-01 00:00:00