Assignment No.

4
Nutrigenomics

Submitted by: Hajra Qayyum (MBI173001)

Submitted to: Dr. Marriam Bakhtiar
Dated: 18th December, 2017

Department of Bioinformatics and Biosciences

Capital University of Science and Technology, Islamabad
 Nutrigenomics and Metabolic Diseases

1. Introduction

Food intake and the environment are the two main factors that affect the health or illness of an
individual. Studies in nutritional area have increased the understanding of how to maintain
healthy a group of individuals that live in different dietary conditions. However, after the
conclusion of the Human Genome Project (HGP), new insights about the influence of nutrients
into people’s diet were postulated, which included (i) will gene expression in response to
metabolic process, at cellular level, influence the health of an individual? (ii) Are gene
expression and metabolic response the result of the interaction between genotype and
environment/nutrient? (iii) Understanding how this interaction process occurs between gene and
nutrient could lead to the prescription of specific diets for each individual. Hence, in order to
answer those questions, Nutrigenomics was introduced. The studies on Nutrigenomics are
focused on the effects of the nutrients over the genome, proteome, and metabolome, as illustrated
in Figure 1.

2. Definition

“Nutrigenomics is the area of nutrition that uses molecular tools to search, access, and
understand the several responses obtained through a certain diet applied between individuals or
population groups.”
3. Nutrient-Gene Interaction in Life-Style Associate Diseases
3.1. Nutrient Interaction in Diabetes

Diabetes mellitus (DM) is a complicated lifestyle associated metabolic disease designated with

alteration in insulin secretion as well as function, or both resulting in hyperglycemia. A long-
term complication resulted in failure and dysfunction of multiple organs such as heart, kidneys,
nerves and blood vasculature. Globally, the prevalence of diabetes is 8.3%, affecting 387 Million
world population and expected further increase upto 592 million by 2035. In general, the diabetic
cases are categorized into two type’s i.e. type 1 (T1DM) and type 2 (T2DM). T1DM is an
autoimmune disease results from destruction of pancreatic β islets by T lymphocytes infiltration
and consequent loss of β cells along with deficiency in insulin secretion. At the onset of disease
about 70% of cells are damaged. However, T2DM is the most prevalent type of complex disease,
which accounts for > 90% diabetic cases. A number of factors like insulin deficiency, insulin
resistance, β cell dysfunction, impaired insulin signaling and oxidative stress associated with this
disease that leads to complications like neuropathy, retinopathy, nephropathy, macro- and micro
vascular conditions. DM is more commonly among peoples between 40 and 59 years of age.
Several factors such as genes & diet, metabolic profile, environmental changes and their
interactions plays crucial role in the disease progression. ‘Omics’ approaches have been
extensively used in exploring the impact of the dietary ingredients upon gene functioning. These
approaches enable us to find new targets like genes, proteins and their interactions with nutrients
The nutrient gene interaction studies are important to understand the associated factors, in the
etiopathogenesis of metabolic syndromes. These factors modulate the gene expression directly or
by activating various signalling molecules of complex metabolic pathways.

3.2. Nutrients-gene Interaction in Cardio Vascular Diseases

Cardio Vascular Diseases (CVD) is characterized by formation of intimal lesions due to lipid
deposition, inflammatory response, and fibrosis and cell death in the blood vessels. CVD is the
major cause of mortality, according to WHO report. Global estimations revealed that, it is
responsible for 17.5 million deaths in 2012 and representing 31% of all global deaths. Nutrition
plays important role in the management and prevention of CVDs. Genes responsible for the
metabolism and biosynthesis of lipids includes Arachidonate 5-lipoxygenase (ALOX5), fatty
acid synthase (FASN), apolipoprotein E (APOE), lipoprotein lipase (LPL), peroxisome
proliferator activated receptors (PPARs) etc, which can be modulated in a protective manner by
shift to a healthy diet. 

3.3. Diet and Inflammation

Nutritional composition of diet systems are known to affect the inflammatory process as a result
of immune response modulation either by alteration of gene expression or interfering into the
signaling cascade. Inflammation is a biological response of human body against any invasion or
injuries, which may be acute (self-healing, short term) or chronic (required medication, long
term). Later inflammation type can last for years and in due course lead to several diseases like
some cancers, intestinal allergies, atherosclerosis etc. In a recent study, researchers have found
that nutrients and certain food items influence inflammation. Inflammatory process is regulated
by immune system, in which several immunological mediators plays significant role.
Curcuma longa (turmeric) well known golden spice has long been in use as Ayurvedic medicine
against inflammatory conditions. It contains number of bioactive compounds, however,
‘curcumin’ is a major metabolites that accounts for numerous pharmacological activities i.e.
antioxidant, antimicrobial and strong antiinflammatory properties. Evidences are available that
advocate curcumin as a highly pleiotropic molecule, capable of interacting with molecular
targets of inflammation. It was reported to be a highly potential therapeutic agent not only for
inflammatory conditions, but also in certain types of cancers. In rat animal model, curcumin was
shown to have a preventive and therapeutic effect in gastric ulcer disease by acting as a strong
inhibitor of H+, K+-ATPase activity. It downregulated the acetylation of histone H3, thereby
inhibiting the transcription and expression of H+, K+-ATPase gene [87]. Curcumin strongly
inhibits the expression of LPS-induced inflammatory mediators along with IL-6, TNF-α and
COX-2 mRNAs in macrophages via modulating the expression of cytokine signaling-1(SOCS-1
and 3) and p38 MAPKsuppressors. Further amendment of nuclear translocation prevents the
inhibition of LPS-induced SOCS-1 and -3 expressions and activation of p38 MAPK kinase.
Recent in vitro, in vivo and human clinical investigation on curcumin (diferyloylmethane) orally
bioavailability and safety revealed that it inhibits TNF-α action and its production. Curcumin
also showed promising role in the prevention of Helicobacter pylori induced inflammation. H.
pylori infection activates a sequence of gastric alterations with induction of gastric mucosa
inflammation, which some time may evolves to gastric cancer. Curcumin exerted a significant
antiinflammatory effect and even attenuate inflammation process by amending the expression of
toll-like receptors (TLRs) and myeloid differentiation primary response gene 88 (MyD88). It is a
promising example of nutritional approach in the prevention of H. pylori induced inflammation.
Vitamin A supplementation proved beneficial against number of inflammatory conditions
including various skin related disorders and various precancerous as well as cancerous states.
Retinoid, a derivative of vitamin A, is known to inhibit neoplasm and improve immune system.
Owing to retinoic acid treatment, a significant increase in expressions of toll-like receptor 4
(TLR4) gene with decreased level of IL-1b β in mammary gland and NF-kappa B DNA binding
activity was observed in lipopolysaccharide (LPS) induced mastitis rat model and mammary
epithelial primary cell cultures . It was deduced from the results that retinoic acid due to
suppression of TLR4/NF-kappa B signaling attenuated the LPS induced inflammatory response.
 Table 1: Interaction between nutrient, gene and their functions in diabetes

Table 2: Interaction between nutrient, gene and their functions in CVD

Table 3: Interaction between nutrient, gene and their functions in inflammation

4. Nutrigenetics and Personalized Nutrition

Phenylketonuria (PKU) was the first genetic disease in which a gene-diet interaction was
described. This condition is a good example of how a single nutrient can be used to manage
genetic predisposition to a monogenic disease. People with PKU lack the enzyme required to
metabolize phenylalanine, an essential amino acid found in dairy, meat, fish, nuts and pulses,
with the result that dangerous levels of phenylpyruvic acid may build up which are toxic to the
brain Thus, individuals with PKU need to stick to a low phenylalanine diet for life to avoid PKU
symptoms. Coeliac disease, an inflammatory condition which results from intolerance to dietary
gluten, is an example of how personalized nutrition can potentially work. High concordance rates
from twin studies indicate a strong genetic influence, but it seems that carrying certain genes
reveals a genetic predisposition to dietary factors rather than disease development. Obesity is
another example of how nutrigenetics can be used to personalize an individual’s diet with a view
to improving long term weight management. A recent pan-European study investigated the
attitudes of consumers towards genetic testing and personalized nutrition. The results of this
study were encouraging, with 66% of respondents willing to undergo genetic testing and 27%
willing to adhere to a personalized diet. Interestingly individuals with MetS and T2DM related
health conditions were particularly positive toward nutrigenetic intervention. These findings are
encouraging for the future application of genome-customized diets for obesity, MetS and T2DM
prevention and therapy following personalized approaches. However, as success or failure of any
new technology is consumer driven, consumer research in the application of personalized
nutrition is essential.

5. Conclusions
Some recent novel nutrigenetic data in the context of metabolic disease have been presented,
which suggest that certain nutrients, in particular dietary fatty acids, may have the potential to
modify the genetic predisposition to these diet-related conditions. While this review has focused
on dietary fat, more holistic methods which incorporate an individuals’ diet or dietary patterns,
rather than selecting individual dietary components, need to be developed to advance the state of
the art. Moreover, other modifiable environmental factors which interact with the diet should be
considered in gene-environment studies (i.e., physical activity, alcohol intake, and smoking
status) across a range of metabolic conditions. Nevertheless current data provides proof of
concept. The shift towards “personalized” nutritional advice is an attractive proposition.
Nutrigenetics has the potential to change diet-related disease prevention and therapy. While
recent advances in high-throughput genetic analysis have improved our understanding of the
contribution of genetics to metabolic health and disease, the molecular mechanisms underlying
many of these gene-nutrient interactions remain unclear. Functional studies are needed to
ascertain their biological significance and potential clinical utility. Nutrigenetics is just one piece
in a very complex jigsaw, which needs to move forward with nutritional science in order to
translate observational findings into molecular mechanisms. The combined application of
nutritional and genetic epidemiology with metabolite and molecular profiling at the gene,
transcriptome, proteome and metabolome level to define an individuals’ metabotype will be
crucial in this regard. Such concerted actions, using larger study cohorts and collaborative
research efforts across different disciplines may lead to the identification of sensitive/responsive
metabotypes (i.e., modifiable by dietary fatty acids or other nutrients). The challenge for current
and future research is validation and translation of nutrigenetic findings, which may provide the
basis for successful personalized and public health approaches for metabolic disease prevention.

6. References

1. Phillips CM. Nutrigenetics and Metabolic Disease: Current Status and Implications for
Personalised Nutrition. Nutrients. 2013;5(1):32-57. doi:10.3390/nu5010032.
2. Rana S, Kumar S, Rathore N, Padwad Y, Bhushana S. Nutrigenomics and its Impact on Life
Style Associated Metabolic Diseases. Current Genomics. 2016;17(3):261-278.
doi:10.2174/1389202917666160202220422.