Obesity and Asthma: Genetics and Nutrigenetic Response to Omega-3 Fatty Acids

Summary

Principal Investigator: Jason E Lang
Abstract: DESCRIPTION (provided by applicant): Obesity increases the risk for asthma diagnosis in children and adults. With obesity on the rise, a better understanding of this association may become critically important to public health. The goals of this proposal are to 1) address important etiologic questions in obesity-related asthma and, 2) allow Dr. Lang to develop expertise in the fields of pediatric asthma clinical trials and pharmacogenetics. The candidate became interested in the link between obesity and asthma during his work with Dr. Stephanie Shore at the Harvard School of Public Health. He is now interested in translating this basic science experience into the fields of pediatric asthma, pharmacogenetics and nutrigenetics. Dr. Lang is currently working as a pediatric pulmonologist at the Nemours Children's Clinic (NCC) in Jacksonville, Florida. In the spring of 2009, he started the core coursework needed to earn a Master's degree in Public Health. A Career Development Award would allow Dr. Lang to finish his MPH with special emphasis on Epidemiology, Statistical Genetics, Pharmacogenetics and Nutrition. NCC will furnish an excellent training environment for clinical and translational research due to its dedicated Biomedical Research Department, the Center for Pharmacogenomics (directed by his mentor, Dr. Lima), and its close affiliation with the American Lung Association - Asthma Clinical Research Centers Network. Dr. Lang is interested in determining if the increased risk of asthma among the obese stems from a genetic origin shared by both conditions. We propose to interrogate three high quality genotype-phenotype extant datasets from 3 past ALA-ACRC asthma trials as well as 3 matched cohorts of non-asthmatics for plausible candidate gene polymorphisms that associate with obesity. Genetic polymorphisms associating with obesity will be further evaluated for association with asthma, and then assessed for replication among publically available genotype/phenotype samples on the database of Genotypes and Phenotypes (dbGaP) maintained by National Center for Biotechnology Information. In aim #2, we will determine the impact of fish oil-derived Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) on asthma control among obese asthmatics. These omega-3 fatty acids have been shown to: reduce inflammation important to asthma and improve asthma outcomes in an inconsistent manner across previous smaller studies - results that are consistent with a pharmacogenetic influence. There exists evidence that omega-3 fatty acid response displays a pharmacogenetic response related to ALOX5 genotype. Dr. Lang's preliminary data suggests that obese individuals are at greater risk for possessing this same ALOX5 variant and thus obese asthmatics may be more responsive to fish oil. We will determine (in a sub-aim) if there exists an ALOX5 genotype-related response effect with fish oil. This will be the largest clinical trial of omega-3 fatty acid for the treatment of asthma, and the first applying pharmacogenetic/nutrigenetic analysis. This proposal is designed in a fashion to: 1) be extremely cost-effective (since we utilize extant DNA samples from our affiliation with the ALA-ACRC, and since all costs associated with completing the proposed education and research that are not supplied through the award will to be borne by the Nemours Foundation), and 2) equip the PI with the genetic, pharmacogenomic, and clinical trials expertise to become an successful translational scientist. Furthermore, the results of this project may add to the pursuit of personalized asthma care and direct future investigation into the etiology of obesity-related asthma. This project, through our ALA-ACRC affiliation, may be well positioned to transition into a large multicenter asthma trial.
Funding Period: 2010-05-01 - 2015-04-30
more information: NIH RePORT

Top Publications

  1. pmc Nutrigenetic response to omega-3 fatty acids in obese asthmatics (NOOA): rationale and methods
    Jason E Lang
    Division of Pulmonary and Sleep Medicine, Nemours Children s Hospital, Orlando, FL, USA
    Contemp Clin Trials 34:326-35. 2013
  2. pmc ALOX5 polymorphism associates with increased leukotriene production and reduced lung function and asthma control in children with poorly controlled asthma
    E Mougey
    Center for Pharmacogenomics and Translational Research, Nemours Children s Clinic, Jacksonville, FL 32207, USA
    Clin Exp Allergy 43:512-20. 2013

Detail Information

Publications2

  1. pmc Nutrigenetic response to omega-3 fatty acids in obese asthmatics (NOOA): rationale and methods
    Jason E Lang
    Division of Pulmonary and Sleep Medicine, Nemours Children s Hospital, Orlando, FL, USA
    Contemp Clin Trials 34:326-35. 2013
    ..NOOA may lead to a new therapeutic treatment strategy and greater understanding of the mechanistic role of diet in the pathogenesis of asthma...
  2. pmc ALOX5 polymorphism associates with increased leukotriene production and reduced lung function and asthma control in children with poorly controlled asthma
    E Mougey
    Center for Pharmacogenomics and Translational Research, Nemours Children s Clinic, Jacksonville, FL 32207, USA
    Clin Exp Allergy 43:512-20. 2013
    ..A promoter polymorphism in the 5-lipoxygenase gene affects gene expression and response to asthma therapy, but its impact on disease control remains unclear...

Research Grants30

  1. Pharmacogenomics of Preterm Birth Prevention and Treatment
    TRACY ANN MANUCK; Fiscal Year: 2013
    ..These advances may result in individualized preterm birth interventions, which in turn could lower the overall rate of both primary and recurrent SPTB and its corresponding neonatal morbidity and mortality. ..
  2. Factors Modifying the Toxicity of Methylmercury in a Fish-Eating Population
    Philip W Davidson; Fiscal Year: 2013
    ..Rand's laboratory while genes and genetic variations in those genes linked to MeHg tolerance in Drosophila by Dr. Rand can help focus Dr. Broberg's work on SNPs that appear particularly important to the neurotoxicity of MeHg. ..
  3. Molecular mechanism of omega-3 response
    JAMES T BRENNA; Fiscal Year: 2013
    ..Human genetic variation and metabolic conditions responsive to omega-3 LCPUFA supplementation will be identified. ..
  4. Genome-wide interrogation of genetic signatures for glucocorticoid sensitivity
    Rong Stephanie Huang; Fiscal Year: 2013
    ..The long term goal is to identify patients, using their genetic make up, that are at risk for toxicities and non- response associated with GCs with the intent to reduce their chances of an adverse event and improve their care. ..
  5. INTEGRATIVE PHARMACOGENOMICS OF LEUKOTRIENE INHIBITION IN ASTHMA
    Kelan G Tantisira; Fiscal Year: 2013
    ....
  6. Semi-volatile PCBs: Sources, Exposures, Toxicities
    Larry W Robertson; Fiscal Year: 2013
    ..These data and dietary studies in the last Aim will provide a scientific basis for risk assessment and advice for stakeholders with the ultimate goal to protect highly-exposed individuals and populations. ..