1 Obesity, Nutrition, Nutrigenonmics – OH MY! Karen L. Edwards, Ph.D.Director, UW Center for Genomics and Public HealthDepartment of Epidemiology and Institute for Public Health GeneticsSchool of Public Health and Community MedicineUniversity of Washington
2 ObjectivesBe familiar with the evidence for genetic influences on obesityBe able to define nutrigenomicsUnderstand current limitations of nutrigenomic testing
3 Outline Background Genetics of Obesity Animals Humans Environmental effectsNutrigenomicsWhy the interest?Current products and examplesWhy the concern?Moving from promise to practice5. Summary and Conclusions
4 Public Health Importance MortalityIncreased risk of premature deathMorbidityDiabetes, Heart disease, Hypertension, some Cancers, Breathing Problems, Ischemic Stroke, Arthritis, and Reproductive ComplicationsPrevalence59 million (30%) Americans are obese (BMI>= 30)Rates are increasing faster than ever (epidemic proportions)
5 Risk Factors for Obesity Diet: high calorie and low nutrient dense foodsPhysical InactivityAgeSocioeconomic statusCertain medical conditions and medicationsRaceSmoking cessationFamily HistoryGenetic susceptibility
7 Evidence for genetic influences: Humans Familial aggregation- familial clustering of obesity in familiesTwin Studies- greater concordance among MZ twins compared to DZ twinsFamily Studies- variety of “statistical models” consistent with genetic influences
8 The Search for Obesity Susceptibility Genes “I found one! I found one!”Kenneth M. Weiss & Joseph D. Terwilligernature genetics • volume 26 • October 2000
9 Candidate Genes and Single Gene Disorders: Chromosomal Location Image adapted from:Loos, R. J. and C. Bouchard (2003). J Intern Med 254(5):
10 Genetics of Human Obesity Common form(s) of obesity are likely due to complex interactions between genes and environment- body fat pattern- appetite regulation- other pathwaysRare monogenic forms do not account for majority of cases
11 Trends in ObesityFrom the CDC website: BRFSS Trends Data
12 Trends in ObesityFrom the CDC Website: NHANES Study Data
16 Nutrigenomics vs. Nutrigenetics “Nutrigenomics refers to the application of genomics in nutrition research, enabling associations to be made between specific nutrients and genetic factors, e.g. the way in which food or food ingredients influence gene expression…Nutrigenomics should facilitate greater understanding of how nutrition affects metabolic pathways and how this process goes awry in diet-related diseases.” Chadwick R. (2004) Proceedings of the Nutrition Society 63:Nutrigenetics“Nutrigenetics is the study of individual differences at the genetic level influencing response to diet. These individual differences may be at the level of single nucleotide polymorphisms rather than at the gene level…It is envisaged that nutrigenetics may lead to individualized dietary advice.” Chadwick R. (2004) Proceedings of the Nutrition Society 63:
17 Nutrigenomics vs. Nutrigenetics “Nutrigenomics attempts to study the genome-wide influences of nutrition…[and] aims to identify the genes that influence the risk of diet-related diseases on a genome-wide scale, and to understand the mechanisms that underlie these genetic predispositions.” Muller M & Kersten S. (2003) Nature Reviews Genetics 4:Nutrigenetics“Nutrigenetics examines the effect of genetic variation on the interaction between diet and disease or on nutrient requirements. Genetics has a pivotal role in determining an individual’s risk of developing a certain disease.” Muller M & Kersten S. (2003) Nature Reviews Genetics 4:
18 Nutrigenomics vs. Nutrigenetics “Nutrigenetics embodies the science of identifying and characterizing gene variants associated with differential responses to nutrients, and relating this variation to disease states.” Mutch D, et al. (2005) FASEB Journal 19:“Nutrigenetics examines the effect of genetic variation on the interaction between diet and exercise. This includes…gene variants associated with, or responsible for, differential responses to nutrients.” Ordovas J & Mooser M. (2004) Current Opinion in Lipidology 15:Nutrigenomics“Nutrigenomics describes the use of functional genomic tools to probe a biological system following a nutritional stimulus that will permit an increased understanding of how nutritional molecules affect metabolic pathways and homeostatic control.” Mutch D, et al. (2005) FASEB Journal 19:“Nutrigenomics focuses on the effect of nutrients on the genome, proteome, and metabolome.” Ordovas J & Mooser M. (2004) Current Opinion in Lipidology 15:
19 Nutrigenomics & Nutrigenetics: Two Sides of a Coin Mutch D, et al. (2005) FASEB Journal 19:
20 Nutritional GenomicsThe study of how different foods can interact with particular genes to increase the risk of diseasessuch as type 2 diabetes, obesity, heart disease and some cancersGoal: Use of personalized diets to prevent or delay the onset of disease and optimize and maintain human health
21 Nutritional Genomicsvan Ommen B. (2004) Nutrition 20:4-8.
22 Why the interest? Improve health of populations United States Globally Improve athletic performanceWeight lossPotential economic impactFunctional food and dietary supplements is currently a $40 billion industryThe focus on nutrigenomics could mean an $80 billion dollar industry in 7-10 years
23 What is the evidence? Single Gene Disorders PKU Lactose intolerance Complex conditionsGenes involved in susceptibility to complex diseases have been identifiedNutritional environment modifies the expression of genesMetabolism of nutrients may vary by genotype, ultimately affecting healthSingel gene disorders, good evidence for effective nutrition intervention based on genotypeComplex conditions – although the evidence is increasing, evidence is less clear cut, -- efficacy has not been established and there will be challenges to doing thisgene x e is difficultLarge samplesreplicaiton
24 What is the public health implication? Can we use this information along with our increasing knowledge of the genetics of obesity for public health applications?Obesity epidemicSingel gene disorders, good evidence for effective nutrition intervention based on genotypeComplex conditions – although the evidence is increasing, evidence is less clear cut, -- efficacy has not been established and there will be challenges to doing thisgene x e is difficultLarge samplesreplicaiton
25 Direct to Consumer Marketing Health ClubsVending MachinesInternetRetail stores
28 Weight LossDNA Diet Builds Customized Weight-Loss PlanOne-size-fits-all diets could be a thing of the past.NBC station KNSD in San Diego reported that a handful of bio-tech companies are promising a high-tech recipe for losing weight and eating better. The newest weight-loss plan is a customized diet based on your DNA. The DNA diet is a personalized meal plan that claims to be based on your unique genetic blueprint.Katzin claims that based on your DNA profile she can “determine whether someone should increase the amount of folic acid, B-6 or B-12, for example. So, we would choose foods that are rich in those supplements.”… “interprets the data and makes a customized meal plan. Her suggestions range from “ taking more vitamins to eating more meat.”
29 Diet Design, One Pair of “Genes” at a Time Health: You Are What You Eat Oct. 31, 2005 issue - Bruce Morrill is something of a health nut. So when his nutritionist suggested he take a $695 DNA test so she could individualize his diet plan, Morrill, a 42-year-old UPS driver from Reno, Nev., agreed.
30 Currently in the United States, no regulations are in place for evaluating the accuracy and reliability of genetic testing. Most genetic tests developed by laboratories are categorized as services, which the Food and Drug Administration (FDA) does not regulate. This lack of government oversight is particularly troublesome in light of the fact that a handful of companies have started marketing test kits directly to the public. Some of these companies make dubious claims about how the kits not only test for disease but also serve as tools for customizing medicine, vitamins, and foods to each individual's genetic makeup. (doegenomes.org)Genetic testing to identify alleged risk factors that have no proven corrective measures is simply a waste of money. As noted by Helen Wallace, Ph.D., Deputy Director of GeneWatch UK: "For most people, tailoring your diet to your genetic make-up is about as scientific as tailoring your diet to your star sign."
31 Sciona International company previously based in the UK Personalized health and nutrition recommendationsProducts were available through retail storesGeneWatch UK called on retail stores to stop offering these testsCurrently based in Boulder, ColoradoLaunching a campaign in 4 test marketsPartnerships with retail stores and local health care system
33 Lund Foods CEO: “…plan is to create a link between the evaluations performed by Sciona and his stores’ food experts, which have long provided consumers with diet and nutritional advice and information.”Today Food Editor: “The idea, which is a good one, is to help shoppers understand what they can do in their daily food choices to either maintain their good health or help correct certain genetic defects that the test may have identified.”
34 Heart Health“Analyzes thirteen of your genes that may play an important role in determining how your body manages overall heart health”“…assesses nine key diet and lifestyle action areas”
35 Bone Health“Analyzes four of your genes that may play an important role in determining how your body manages overall bone health“..assesses seven key diet and lifestyle action areas”
36 Insulin Resistance“Analyzes five of your genes that may play an important role in determining how your body manages overall insulin resistance”“..assesses five key diet and lifestyle action areas”
37 Genetic Assessment for Antioxidant and Detoxification “Analyzes six of your genes that may play an important role in determining how your body manages overall antioxidant/ detoxification health”“..assesses four key diet and lifestyle action areas”
38 Inflammation Health“Analyzes six of your genes that may play an important role in determining how your body manages inflammation”“..assesses four key diet and lifestyle action areas”
40 Consumer Demand?Sciona claims to have sold 10,000 kits in Europe, Asia and the USCurrent use is likely limited to those who can afford to payHealthSyles Survey indicates that only 14% of US population are aware of these tests, and only 0.6% have used a test- age and income are associated with awareness(Goddard et al., GIM 2007;9:510-7)
41 Why the Concern?Currently in the United States, no regulations are in place for evaluating the accuracy and reliability of genetic testing. Most genetic tests developed by laboratories are categorized as services, which the Food and Drug Administration (FDA) does not regulate. This lack of government oversight is particularly troublesome in light of the fact that a handful of companies have started marketing test kits directly to the public. Some of these companies make dubious claims about how the kits not only test for disease but also serve as tools for customizing medicine, vitamins, and foods to each individual's genetic makeup. (doegenomes.org)Genetic information is unlike other health information, in that it also provides information about your family membersGenetic testing to identify alleged risk factors that have no proven corrective measures is simply a waste of money. As noted by Helen Wallace, Ph.D., Deputy Director of GeneWatch UK: "For most people, tailoring your diet to your genetic make-up is about as scientific as tailoring your diet to your star sign."
42 “Buyer Beware” A recent report by the Government Accountability Office highlighted a few of the concerns with four examples of DTCnutrigenomic tests. The GAO report raised concerns thatthe tests may mislead consumers by making unsound and ambiguouspredictions about health risks. In addition, the testresults frequently include recommendations for the consumerto purchase dietary supplements that may be significantlyoverpriced compared with similar products available througha supermarket or pharmacy and that may, in fact, be harmfulfor some individuals.
43 Potential Benefits Increased focus on a healthy diet and lifestyle Motivate positive behavior changeIncreased awareness of risk of certain conditionsImproved health and quality of lifeFocus on preventionDecreased morbidity and premature mortalityReduced health care costsIdentify subgroups who might be particularly responsive or resistant to environmental (dietary) interventionBetter understanding of the mechanisms involved in disease susceptibility
44 Potential HarmsAttention is drawn away from other modifiable risk factorsDecreased use of other servicesFalse sense of securityFocus on specific nutrients/foodsIneffective or harmfulMisleading claimsDilute or contradict public health messages
45 Potential Harms, cont.Increased costs associated with personalized diets and designer foodsTargeting vulnerable populationsConcerns surrounding confidentiality, insuranceBiobanking of samples, informed consentUnintended consequences
46 From Promise to Practice Consistent evidenceEvidence for clinical utility – added valueUnderstand how information is usedCulturally specific translationThoughtful integration based on evidenceHolistic approachAddress ELSI issues prior to integrationAccess to services and “treatment”What will be required to move this into practiceBefore we can do evidence based reviews need good quality studiesNeed to evaluate gxe
47 Summary Potential is exciting Range of opinions regarding readiness of current applicationsMany parallels to pharmacogenomicsDr. Arno Motulsky: “ the total promise of PGX is often overstated and is unlikely to lead to a revolution in therapeutics”May provide benefits to some individuals, but probably not as broadly as currently predicted
48 Conclusions Obesity is influenced by both genes AND environment Obesity is associated with poverty, SES and educationDiet is importantHigh-fat energy-dense foods are often the cheapest options for the consumerHealth foods cost moreNutrigenomic testing is not ready for prime time
49 UW Center for Genomics and Public Health Funded as part of the ASPH/CDC/ATSDR cooperative agreementOffice of Genomics and Disease PreventionCenters for Disease Control and PreventionPlease complete our evaluation
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