Nutrigenomics

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Nutrigenomics

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The study of how foods interacts with our genome:
How dietary chemicals alter gene expression
How genetic differences (gene variants) affect the metabolic and physiologic response to food
How diet-regulated genes may play a role in the incidence, progression, or severity of chronic disease
How dietary interventions based on knowledge of genotype (i.e., "personalized nutrition") can be used to prevent, mitigate or cure chronic disease

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Diet Gene Interactions

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Increase (decrease) efficiency of macro and micro nutrient absorption or metabolism
In the setting of a modern-day diet, alleles that modulate nutrient absorption could:
Induce nutrient deficiency
Increase the salutary effects of nutrients
Induce nutrient toxicity
Increase the disease protective (or inducing) effects of specific nutrients in carriers

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Diet and Gene Evolution

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Lactase and dietary calcium absorption
T2R mutations, taster status, and nausea
Apo A4-S and dietary DHA secretion in milk

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Lactase

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A -disaccharidase located in the brush border of intestinal enterocytes
High levels appear shortly after birth
mRNA and protein levels fall sharply at the time of weaning in all mammals
In most human populations lactase levels fall throughout childhood and are low by the end of adolescence

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Lactase Persistence

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In some populations there is a high frequency of adult lactase persistence
Autosomal dominant trait with north south, eastwest frequency gradient
These populations have a historically high intake of milk and dairy products
Mapped to a SNP (C/T-13910) upstream of the lactase gene on chromosome 2

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Taste and diet/gene evolution

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Ability to sense different tastes is mediated by five families of lingual taste receptors
Bitter taste identifies potentially toxic substances, and leads to their rejection
Conditioned taste avoidance -> aversion
Advantage of reduced bitter sensitivity ?
Many fruits and vegetables contain bitter, yet potentially beneficial, phytochemicals (e.g., flavonoids and glucosinolates)

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T2R polymorphisms

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There is a very wide individual variation in the ability to perceive bitter tastes
Taster trait (T+) is Mendelian dominant
Homozygous (TT) – Supertaster (ST)
Heterozygous (Tt) – Taster (T)
Homozygous (tt) – Non-Taster (NT)
Trait caused by polymorphisms in theT2R family of G-protein coupled receptors
~ 35% of USA population are non-tasters

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Diet and Gene Evolution Nausea

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Nausea and vomiting provide a second tier of protection against toxin ingestion
Nausea stops further toxin ingestion, and vomiting eliminates toxins from the GI tract
Nausea susceptibility is highly variable
~50% of the population has  susceptibility
Did the non-taster and nausea-susceptibility traits co-evolve in a reciprocal manner?
In settings where the NT trait conferred an advantage,  nausea susceptibility may have maintained protection against other toxins

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Diet and Gene Evolution Apo A IV S Allele

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SNP encodes a T347S substitution
S-allele frequency = 20-25% worldwide, suggesting that it is an ancient allele
Associated with
 Post-prandial chylomicron clearance
 BMI and  Adiposity
More rapid chylomicron clearance may increase the flux of dietary fat into milk
The S-allele may have evolved to confer a neonatal nutritional advantage

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thrifty gene hypothesis

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Proposed in 1962 by geneticist James Neel
Postulates that certain genes evolved to maximize metabolic efficiency and nutrient storage
In ancient times, thrifty genes would have conferreda selective advantage during periods of famine.
However, in abundant times, thrifty genes predispose carriers to diseases caused by dietary excess
Ethnic groups with a history of food scarcity will have undergone greater evolutionary pressure, and may harbor more thrifty genes than other populations.

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Genomics and DIetary Rx

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Assess present macro and micro nutrient status and future requirements
Identify noxious foodstuffs and enable portioning for symptomatic relief
Guide prescription of foods and diets for disease treatment and prevention
Predict response to dietary intervention