Biological Markers: New Horizons from -omics Jose M. Ordovas
JM-USDA-HNRCA at Tufts Univ. Boston, MA
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Current and Future Practice of Disease Prevention/Therapy 2004
circa2010 Predisposition Focused Screening Early detection
Personalized Prevention/Therapy Therapeutic Monitoring
DiagnosisGlobal Advice/Therapy Based on Classical and New
Biomarkers Based on Genetics Public Health Policy/
Genotype/Phenotype Associations: Lack of Consistency
Meta-analyses of population-based studies of effect of Gly188Glu,
Asp9Asn, Asn291Ser, and Ser447Ter substitutions at the LPL locus on
plasma triglycerides. Wittrup: Circulation, Volume 99(22).June 8,
1999.2901-2907
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LPL, influence of obesity over the phenotypic expression of the
genotype Corella and Ordovas. The metabolic syndrome: a crossroad
for genotype-phenotype associations in atherosclerosis. Current
Atherosclerosis Reports, 2004.
Knock-out mice: the effects on body fat accumulation
Martinez-Botas J, Nat Genet. 2000 Dec;26(4):474-9
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Valencia
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Odds Ratio for obesity according to PLIN genotypes MENWOMEN Lu
et al. Clin Genet 2004: 66: 299310
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Combined effect of the PLIN polymorphisms on weight and BMI
(Valencia) Obese phenotype Lean phenotype PLIN1 PLIN4 PLIN5
PLIN6
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Replication of PLIN Associations Lu et al. Obesity Research,
2004 Lu et al. J Mol Med, 2005
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Weight reduction in response to a low caloric diet depending on
the PLIN (11482G>A ) polymorphism in obese subjects P=0.015 for
interaction detween diet and PLIN
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Current and Future Practice of Disease Prevention/Therapy 2004
circa2010 Predisposition Focused Screening Early detection
Personalized Prevention/Therapy Therapeutic Monitoring
DiagnosisGlobal Advice/Therapy Based on Classical and New
Biomarkers Based on Genetics Public Health Policy/
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Genome Gene Regulation/Expression Metabolism Metabonomics
Chemometrics and Bioinformatics CONTROL LEVELS Organelle Cell
Tissue Organ Biofluid Organism Proteomics Measurement of Biological
Interactions at Different Levels of Biomolecular Organisation:
Systems Biology Transcriptomics Proteins PHENOTYPE AND DISEASE?
ENVIRONMENT
Metabonomics Tools 800 MHz Ultrashielded NMR spectrometer
AVANCE 800 spectrometer with the UltraShield- UltraStabilized 800
magnet at Bruker Application Lab
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900 MHz 1 H 1D NMR Spectrum of Human Urine Nmr radiofrequency
scale in arbitary units Intensity (proportional to micromolar
proton concentration)
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125 128 129 101 102103 104 105 106 107 108 111 112 113114 117
119 120 121 122 123 124 125 128 129 Human Population Response
Vector Analysis: Multivariate Effect of Statin Treatment
PHARMACO-METABONOMICS: EACH LINE REPRESENTS AN INDIVIDUALS RESPONSE
VECTOR CONNECTING PRE-AND POST-TREATMENT Strong % decrease in TRG
Strong % increase in TRG % increase in TRG, LDL, CHOL and HDL (bis
sample trajectory) PC1 Good Responders Poor Responders
subjects
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Pattern Recognition Analysis: Control and Soya Dosed Humans
Systematic metabolic effect of diet
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The New Horizon Remains Obscured by Fog and Obstacles
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Population Studies of appropriate experimental design Clinical
trials of adequate size and quality Genetic associations
Product-specific clinical trials in subjects selected for specific
genetic variants Proper evaluation of benefit (FDA?) Address DTC
genetic testing issues Educate service providers (physicians,
nutritionists) Publish high quality research!! Meeting the
Challenges