Pharmacogenomics Research Today is a free monthly online journal that collates and summarizes the latest research about Pharmacogenomics, including details on pharmacology, designer drugs, customized medicines.

Asthma genetics: personalizing medicine.

Warrier MR, Hershey GK

Institute for Personalized and Predictive Medicine and Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA. Gurjit.Hershey@chmcc.org

Asthma is a chronic inflammatory lung disease that leads to significant morbidity, mortality, and economic burden. The clinical symptoms, which are a result of airway inflammation and reversible airway obstruction, have led to the mainstay of therapies for asthma: anti-inflammatory medications and bronchodilators. However, the efficacies of the various classes of medications are not equal among all patients and may be affected by asthma phenotypes, environmental exposures, and genetic differences. Similarly, the risk for developing asthma and the natural history of the disease show great inter-individual variability due to these same factors. Over the past few decades, much effort has been focused on the genetics of asthma, and investigators have identified more than one hundred potential asthma susceptibility genes, of which at least ten have been replicated in numerous independent studies. In parallel, researchers have also identified genetic factors that impact the pharmacotherapeutic responses to the major classes of asthma medications. While the results of previous studies have been promising, future investigations need to combine genetics, pharmacogenetics, accurate disease phenotyping, and environmental exposures to build the foundation for personalized and predictive medicine for the 21st century. The ultimate goal is to enable physicians to identify those at risk for asthma, intervene to prevent or attenuate the disease, and select the optimal medical regimen for each individual patient. If successful, the resulting paradigm shift in medical practice will lead to improved clinical outcomes and decreased health care expenditures.

Published 30 April 2008 in J Asthma, 45(4): 257-64.
Full-text of this article is available online (may require subscription).

Articles on Pharmacogenomics published 21 April 2008:

Pharmacogenetics: from bench to byte.   Clin Pharmacol Ther, 83(5): 781-7.

Despite initial enthusiasm, the use of pharmacogenetics has remained limited to investigation in only a few clinical fields such as oncology and psychiatry. The main reason is the paucity of scientific evidence to show that pharmacogenetic testing leads to improved clinical outcomes. Moreover, for most pharmacogenetic tests (such as tests for genetic variants of cytochrome P450 enzymes) a detailed knowledge of pharmacology is a prerequisite for application in clinical practice, and both ... [Abstract] [Full-text]

Articles on Pharmacogenomics published 2 April 2008:

Defining drug disposition determinants: a pharmacogenetic-pharmacokinetic strategy.   Nat Rev Drug Discov, 7(4): 293-305.

In preclinical and early clinical drug development, information about the factors influencing drug disposition is used to predict drug interaction potential, estimate and understand population pharmacokinetic variability, and select doses for clinical trials. However, both in vitro drug metabolism studies and pharmacogenetic association studies on human pharmacokinetic parameters have focused on a limited subset of the proteins involved in drug disposition. Furthermore, there has been a one-way ... [Abstract] [Full-text]

Articles on Pharmacogenomics published 19 March 2008:

Pharmacogenetic studies in depression: a proposal for methodologic guidelines.   Pharmacogenomics J, 8(2): 90-100.

Pharmacogenetic studies in mood disorders are rapidly proliferating after the initial reports linking gene variants to treatment outcomes. However, a considerable range of methodologies has been used, making it difficult to compare results across studies and limiting the representativeness of findings. Specification of sampling source (inpatients vs outpatients, primary vs tertiary settings), standardization of diagnostic systems and treatments, adequate monitoring of compliance through plasma ... [Abstract] [Full-text]

Ancillary risk information and pharmacogenetic tests: social and policy implications.   Pharmacogenomics J, 8(2): 85-9.

Some pharmacogenetic tests may provide ancillary disease risk information. To evaluate evidence and assess the social and policy implications of ancillary disease risk information associated with candidate pharmacogenetic variants, We conducted a literature search and abstract review of disease susceptibility studies for each of 42 gene variants potentially associated with drug response. Twenty-two variants (53%) had suggested association with disease risk in at least two studies, and sixteen ... [Abstract] [Full-text]

Articles on Pharmacogenomics published 17 March 2008:

Discovery of genetic profiles impacting response to chemotherapy: application to gemcitabine.   Hum Mutat, 29(4): 461-7.

Chemotherapy is a major treatment modality for individuals affected by cancer. Currently, a number of genome-based technologies are being adopted to identify genes associated with drug response; however, large-scale genetic association applications are still limited. Here we describe a novel strategy based on the genetic and drug response data of the NCI60 cell lines to discover potential candidate genetic variants associated with variable response to chemotherapy. As an example we have applied ... [Abstract] [Full-text]

PharmGKB and the International Warfarin Pharmacogenetics Consortium: the changing role for pharmacogenomic databases and single-drug pharmacogenetics.   Hum Mutat, 29(4): 456-60.

PharmGKB, the pharmacogenetics and pharmacogenomics knowledge base (www.pharmgkb.org) is a publicly available online resource dedicated to the dissemination of how genetic variation leads to variation in drug responses. The goals of PharmGKB are to describe relationships between genes, drugs, and diseases, and to generate knowledge to catalyze pharmacogenetic and pharmacogenomic research. PharmGKB delivers knowledge in the form of curated literature annotations, drug pathway diagrams, and very ... [Abstract] [Full-text]

Human genome variation and pharmacogenetics.   Hum Mutat, 29(4): 453-5.

A recent HGVS-sponsored symposium has examined, for the first time, the possible effects of the discovery of very large and widespread amounts of human genome variation on the emerging fields of pharmacogenetics and pharmacogenomics. This article discusses the effects of the resultant paradigm shifts and raises a number of important questions that need to be considered in order to truly advance the field in a meaningful and significant way. [Abstract] [Full-text]

Articles on Pharmacogenomics published 10 March 2008:

Toxicogenomic analysis of gender, chemical, and dose effects in livers of TCDD- or aroclor 1254-exposed rats using a multifactor linear model.   Toxicol Sci, 102(2): 291-309.

Chronic exposure of Sprague-Dawley (SD) rats to either 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or Aroclor 1254 results in female-selective induction of hepatic tumors. The relative potency of dioxins and polychlorinated biphenyl mixtures, such as Aroclor 1254, is often estimated using the internationally endorsed toxic equivalency (TEQ) approach. Comparing the genome wide changes in gene expression in both genders following exposure to TEQ doses of these chemicals should identify critical ... [Abstract] [Full-text]

© 2005-2008 Pharmacogenomics Research Today. All Rights Reserved.