NUTRITIONAL REQUIREMENTS DEPENDING ON

GENOTYPE

dr. Grace M. K. dr. Regina Tuwongkesong dr. Diza Mehriva H Nirwana

C175222002 C175222010 C175222011 C175222012
 NUTRIGENETIC

identifies how the genetic makeup of a particular individual

co-ordinates his or her response to various dietary nutrients.

reveals why and how people respond differently to the same nutrient.

Together these two approaches promise to deliver a critical part of the scientific knowledge needed

to understand how diet affects the individual humans and eventually nutrigenomics will lead to

evidence-based dietary intervention strategies for restoring health and fitness and for preventing
diet-related disease.
 NUTRIGENETIC

The concept of a “nutritional phenotype” involves the

interconnection between diet and the disease/wellness
balance with the aim to determine relevant genes, proteins, and metabolic pathways
that modulate health status in a certain environment as a starting point to tailor
dietary patterns .

Principles of Nutrigenetics and Nutrigenomics. Elsevier 2020

 Nutrient requirements vary within all human populations and can be modified by
age, sex, and life stage, among other factors.

Human genetic variation is a determinant of nutrient

efficacy and of tolerances and intolerances and has the
potential to influence nutrient intake values

Patrick J. Stover. Food and Nutrition Bulletin, vol. 28, no. 1 (supplement) © 2007
 Single nucleotide
polymorphisms (SNPs)

mapping polymorphic regions of the genome

that control individual phenotypic differences
among the human population.

Specific genetic polymorphisms in human

populations change their metabolic response to diet
and influence the risk patterns of disease as SNPs are
similar to variations in a recipe.

These genetic polymorphisms lead to alteration of the

response to the dietary components by influencing
absorption and metabolism

Nagwa E.A. Gaboon. The Egyptian Journal of Medical Human Genetics (2011)
Patrick J. Stover. Food and Nutrition Bulletin, 2007,
 MAKRONUTRIENT
Protein (1) Lactose Metabolism Oxidative metabolism
The SLC6A6 gene

encoding a protein that transports taurine

to the retina and cardiac muscle.

individuals carrying a rare mutation in the

SLC6A6 gene (NM_003043.5:
expression of the low activity resulting from amino
C.1196G>T) have altered taurine
homeostasis because of the dramatically enzyme lactase-phlorizin acid substitutions,
reduced transporting capacity of the hydrolase encoded by the including the G6PD-202A allele
resulting Gly399Val SLC6A6 protein, 
progressive retinal degeneration and LCT gene
systolic cardiomyopathy.
LCT expression declines 
lactose intolerance
prolonged oral taurine supplementation
corrected cardiomyopathy and improved
vision in affected individual

(1) Gkouskous K K. Nutrition review. 2020

 Carbohydrate intake

Ala67Ala homozygotes AgRP polymorphisms

Carbohydrate intake higher. resistance to fatness and to resistance

for developing type 2 diabetes 
remain unknown

Transcription and translation Inheritance

DNA is transcribed into RNA and then translated DNA is inherited from generation to generation
into proteins, which control cellular activities. and is responsible for passing traits from parents
to offspring.
 Glucose and TCF7L2 polymorphism

Transcription Factor-7-Like-2 (TCF7L2),

• belongs to the T-cell factor/lymphoid enhancer factor (TCF/LEF) family, is the most common
susceptibility gene for type 2 diabetes mellitus (T2DM)

• TCF7L2 rs7903146 polymorphism affected glucose tolerance and free fatty acid metabolism in adults.

• For regulating glucose levels using dietary intervention.

Wang et al. Frontiers in Nutrition. 2022

 Nutrient metabolism
Fructose Metabolism Lactose Metabolism Oxidative metabolism
Twenty-five allelic variants of
the human liver isozyme
aldolase B
impair enzyme activity by altering
Km, kcat,
expression of the low activity resulting from amino
and/or protein stability.
enzyme lactase-phlorizin acid substitutions,
hydrolase encoded by the including the G6PD-202A allele
• Accumulation of fructose-1-
LCT gene
phosphate inhibits glycogen
breakdown and glucose synthesis LCT expression declines 
 in severe hypoglycemia lactose intolerance
• Prolonged fructose ingestion in
infants leads ultimately to hepatic
and/or renal failure and death.
Nutritional Requirements Depending on Genotype
LIPID & ALCOHOL
Lipids & ApoE polymorphism
 Lipids are an essential class of hydrophobic biomolecules
that include phospholipids, sterols, and triglycerides (TG).
 Maintaining energy balance, sustaining vital processes,
controlling food intake, and regulating growth and
reproduction.
 Intake of excessive lipids, such as TG and low-density
lipoprotein cholesterol (LDL), may lead to an increased
risk of metabolic diseases.
 Apolipoprotein E (ApoE) is a polymorphic protein that
functions in lipid metabolism and cholesterol transport

Apolipoprotein (ApoE)
ApoE2 (ε2 haplotype)

ApoE3 (ε3 haplotype)

ApoE4 (ε4 haplotype)

 This haplotype system comprises two non-
synonymous SNPs rs429358 (T/C) and rs7412
(T/C) in the exon of ApoE, where :
 ε2 haplotype is represented by TT,
 ε3 haplotype represented by TC,
 ε4 haplotype represented by CC.
 Lipids and FTO polymorphism
Fat mass and obesity-associated gene (FTO) :
Involved in the expression of fat deposition & metabolism-related hormones and genes, is
the first gene associated with obesity

FTO polymorphism :
 FTO rs9939609 A/A genotype was significantly associated with impaired fasting glucose and
insulin resistance.
 Higher serum leptin & lower high-density lipoprotein levels were observed in the
homozygotes of the FTO rs9939609 risk genotype (AA) compared to those with the TT
genotype in overweight adults (29), suggesting the need of precise interventions for these
high-risk population.
 individuals genetically predisposed to obesity particularly benefit by regulating dietary intake
(30, 31) or following personalized diet
 n-3 PUFA and FADS polymorphism

n-3 PUFA, such as eicosapentaenoic acid
(EPA) and docosahexaenoic acid (DHA) are
essential for maintaining health by
contributing to organ development,
membrane fluidity, and inflammation status
EPA and DHA can be synthesized by
desaturases and elongases through the
PUFA biosynthetic pathway, wherein fatty
acid desaturase (FADS) enzymes including
FADS1 and FADS2, are rate-limiting step
enzymes

Cumulative evidence suggested that

the link between PUFA intake and the
risk of CVD could be altered using
genetic differences in FADS
 P

SUGAR

Serum cholesterol levels are likely to be

more responsive to low-fat and low-
cholesterol diets in carriers of the ε4 allele
 Alcohol Metabolism
 The efficiency of ethanol metabolism varies widely among human ethnic populations.
 ADH encodes the enzyme alcohol dehydrogenase, which oxidizes ethanol to
acetaldehyde; acetaldehyde is subsequently oxidized to acetic acid by the enzyme
aldehyde dehydrogenase encoded by ALDH2.
 Seven ADH genes have been identified and cluster on chromosome 4; all encoded
proteins display distinct catalytic properties and tissue-specific expression patterns.
 ADH and ALDH alleles that predominate in east Asian
populations display signatures of positive selection, and the
expression of these variant alleles results in elevated
acetaldehyde concentrations following alcohol consumption,
which may have conferred advantage by protecting against
parasite infection
GENOTYPE-GUIDED VITAMIN SUPPLEMENTATION
 VITAMIN Identifying & matching individuals to
appropriate dietary supplement according to
their genotype is important

differences in response
to micronutrient optimal health benefits
nutrigenetics & nutritional
supplementation and micronutrient
genomics
according to genetic equilibrium
makeup

reducing the adverse events and financial costs

often associated with excessive ONS
23
Kalliopi K. Gkouskou, 2020
FOLATE & RIBOFLAVIN

Folate is the natural form of vitamin
B9.
folate deficiency is
managed by dietary
insufficient dietary intake
supplements containing
 folate deficiency
folic acid, a stable
synthetic form of folate.
 5,10 5- Predominant form of folate
methylenetetrahydrofolate methylenetetrahydrofolate, in the bloodstream

enzyme 10-methylenetetrahydrofolate riboflavin (vitamin B2)  flavin adenine dinucleotide (FAD)

reductase (MTHFR)

genetically linked to the MTHFR

polymorphism rs1801133 (C/T)

Individuals risk for venous

lower serum 5-
carrying the ↑ circulating thrombosis,
methylenetetrahy
rs1801133 TT homocysteine atherosclerosis, &
drofolate levels
genotype heart disease

Homozygotes for rs1801133 TT require higher folate intake than with the CT or CC genotype 
achieve similar homocysteine levels and protection from cardiovascular pathologies
25
 FOLATE & RIBOFLAVIN
flavin adenine
dinucleotide (FAD)

management
of hypertension
benefits of &
linking cardiovascular
important cofactor disease (CVD)
genotypic
and modulator of the information to risk in
enzymatic activity of ↓ BP > susceptible
folic acid &
MTHFR treatment with individuals
riboflavin (ONS)
state-of-the-art
antihypertensive
drugs
B2 to
hypertensive
individuals +
originating from MTHFR
riboflavin (vit. B2) rs1801133 TT
genotype
Women with the MTHFR rs1801133 TT genotype have
been suggested to be more prone to depression
VITAMIN D
PRIMARY SECONDARY
synthesized in the
human epidermis
Dietary intake
following exposure
to UV-B

Individuals who are genetically predisposed to low 25-

Several polymorphisms have been identified in vit D
hydroxy-vitaminD (25[OH]D) concentrations exhibit an
receptor and vitamin D metabolism  associated
increased risk of developing osteoporosis, sarcopenia,
genes affecting vit D levels and health outcome
autoimmunity, malignancies, or CVD

Some RCTS  a significant reduction in the risk of recurrent adenomas following vit
D supplementation according to vit D receptor genotype

importance of applying genetic information about vit D pathway variants and thus
personalizing dietary vit D ONS
VITAMIN A
catalyzed by the enzyme b-carotene 15,150-monooxygenase (BCMO1)
chemically
β-carotene
stored
retinal
unstable retinol as
retinyl esters

Vit A deficiency
predominantly affects
pregnant or lactating
women and pre-school women and children are
children in developing administered large therapeutic
countries doses of b-carotene or provit A
carotenoids
VITAMIN A

modify the amino acid

sequence of BCMO1 at
residues R267S & A379V

Carriers of the A379V allele  32%

2 nonsynonymous
polymorphisms identified in the
BCOM1 gene, rs12934922 &
rs7501331
reduction in the conversion of β-carotene
to retinol
carriers of both R267S and
A379V alleles have a 69%
reduction
Overview of nutrigenetic evidence concerning personalized nutritional supplementation

Kalliopi K. Gkouskou, 2020

 GENOTYPE-BASED SUPPLEMENTATION OF
MINERALS

Iron

Genome-wide association studies have identified several SNPs

that correlate with variations in serum iron levels.

rs855791 association with red blood cell indices and iron levels, with each T
allele decreasing serum iron, transferrin saturation, mean erythrocyte
hemoglobin, and mean corpuscular volume in an additive manner

The T variant of TMPRSS6 rs855791 encodes a nonsynonymous amino acid

substitution (A736V), which reduces the enzymatic activity of TMPRSS6, and may
lead to iron deficiency

Genotype-guided dietary supplementation in precision nutrition Kalliopi K. Gkouskou,

The rs855791 variant localizes in the coding region of transmembrane protease serine 6
(TMPRSS6) gene

The T variant of TMPRSS6 rs855791 encodes a nonsynonymous amino acid substitution

(A736V), which reduces the enzymatic activity of TMPRSS6, and may lead to iron
deficiency

The assessment of TMPRSS6 genotype in patients with anemic celiac disease could inform the
management of iron deficiency, because carriers of the TMPRSS6 rs855791 TT genotype do not
respond to oral iron therapy, and they should rather be guided to parenteral iron
administration

Genotype-guided dietary supplementation in precision nutrition Kalliopi K. Gkouskou,

 19%–75% of people who
are homozygous for the
Hemochromatosis, an C282Y mutation have
inherited disease associated elevated serum ferritin
with C282Y, H63D, and S65C concentrations
mutations in the HFE gene
involved in iron metabolism

The HFE variations should be

The vast majority of considered particularly for
hemochromatosis cases is linked pregnant women and athletes,
to either homozygous C282Y who require frequent iron
allele mutation or to compound supplementation.
heterozygosity for C282Y and
H63D or S65C mutations

Genotype-guided dietary supplementation in precision nutrition Kalliopi K. Gkouskou,

 Zinc

Zinc (Zn) is required for the synthesis, release, and transport of insulin

Zn homeostasis and responses to supplementation are largely controlled by

SLC39 and SLC30 family members

Genetic variations in SLC30A8 have attracted particular attention, because they

interact with Zn to control glucose levels and insulin responses to glucose.

Genotype-guided dietary supplementation in precision nutrition Kalliopi K. Gkouskou,

Zn supplementation and fasting
glucose levels has been reported
in individuals carrying the glucose-
The major C allele of another SLC30A8
raising A allele of SLC30A8
SNP, rs13266634 (C/T), is associated with
rs11558471 rather than the G
lower early insulin response to glucose
allele
intake, and a higher risk of type 2
diabetes mellitus compared with
individuals carrying the T allele

Genotype-guided dietary supplementation in precision nutrition Kalliopi K. Gkouskou,

 25 selenoproin Improved selenium
Selenium (selenocysteine) status has been linked
to a reduced all-cause
mortality rate, improved
brain function and
immune response.
Redox Protein
regulation Selenium folding

some benefit of attaining

higher serum selenium
levels in reducing the risk of
prostate, lung, colorectal,
Thyroid bladder, and breast cancer
hormone
metabolism

Genotype-guided dietary supplementation in precision nutrition Kalliopi K. Gkouskou,

Selenoproteins include enzymes with important physiological roles, as exemplified by the impact
of selenoprotein gene polymorphisms on disease risk and mortality.

Enzyme antioxidant enzyme glutathione peroxidase has an important rolein reducing

oxidative damage.

Men carrying the GPx1 Variant rs1050450 T allele benefit from supplementation of
selenium as it reduces the level of prostate-specific antigen

Genotype-guided dietary supplementation in precision nutrition Kalliopi K. Gkouskou,

THANK YOU