**3. Nutrigenomic diseases and biomarkers**

Research regarding nutrigenomics is based on the principal of individuals nutrition-gene-disease interaction and how to protect the mankind from endangered non communicable diseases (NCDs) like cardiovascular diseases, obesity, diabetes, respiratory diseases, metabolic syndrome and cancers globally? Such type of NCDs are mediated by exposure of particular food components chronically, these are basically busy junk food eating lifestyle diseases of cities. These kinds of nutritional disorder are detected by biomarkers. It may be some disturbed lipid profiles to check the levels of cholesterol and/or triglycerides, increased blood pressure, or abnormal sensitivity of insulin as indicator of NCDs, like cardiovascular disease or metabolic syndrome. These biomarkers are mainly single proteins or metabolites or certain body functions that leads to be an detector for proteomics and metabolic changes in individuals body may be a causative agent's of a variety of chronic diseases which depends on the particular individuals genotype. The molecular aspects of individuals DNA damage can be diagnosed by a number of complementary ways are as follows: (i) damage to single bases (e.g. DNA adducts such as the addition of a hydroxyl radical to guanine caused by oxidative stress); (ii) abasic sites in the DNA sequence (measurable by use of the aldehyde-reactive probe); (iii) DNA strand breaks (commonly measured using the Comet assay); (iv) telomere shortening (measured by terminal restriction fragment length analysis, quantitative PCR or flow cytometry); (v) chromosome breakage or loss (usually measured using micronucleus cytome assays or metaphase chromosome analysis), and (vi) mitochondrial DNA damage (usually measured as deletions or base damage in the circular mitochondrial DNA sequence). These use of damaged DNAs as a biomarkers were recently validated at various levels based on the nutrient associated evidence (cross-sectional epidemiology and intervention studies) and disease (cross-sectional epidemiology and prospective cohort studies) as reported by Fenech, [8]. The micronucleus assay in cytokinesis-blocked lymphocytes is currently the best validated biomarker for nutritional genomic studies of DNA damage. In addition, a well validated nutrigenomics tool is transcriptomics, it includes the microarray assay to analyze the mRNA copies for all actively transcribed genes. The advantage of this technique is within same time it can analyze the expression level of transcripts, thousands of genes in a single assay. In peripheral blood cells, studies of gene-expression patterns have been shown to be specific for diseased states. Whereas, Martin et al., [22] noted that disease-specific gene-expression patterns in blood cells have been identified for breast tumors and leukemia was revealed by Valk et al., [23], and those patterns now used as biomarkers for the detection of diseases.

#### **4. Gene-diet-disease interaction**

SNPs (Single nucleotide polymorphism) or SNVs (single nucleotide variants) are most widely acceptable markers now a days, responsible for genetic variation. Genotypic variations can be detected by SNPs or SNVs, and we can prescribe proper diet plan to avoid non communicable diseases (NCDs) like cardiovascular diseases,

**13**

*Nutrigenomics: An Interface of Gene-Diet-Disease Interaction*

obesity, diabetes and cancers. In this context, Ramos-Lopez et al., [24] revealed the sweet taste receptor (TAS1R2) related to taste perception and Ramos-Lopez et al., [25] depicted cluster of differentiation 36 (CD36), were associated with dyslipidemia in the peoples of Mexico, consume high amounts of carbohydrates and fats respectively. In addition, common variants of genes which regulate homocysteine metabolism, like methylene tetra hydrofolate reductase (MTHFR) and methionine synthase (MTR), are linked with the increased risk for breast cancer among individuals who intakes lower amount of folate, vitamin B6, and vitamin B12 [26]. The status of Vitamin D show polymorphism among the population and have the ability to modulate various metabolism in the organism [27]. Interestingly, the SNPs of the vitamin D receptor (VDR) gene, affect the availability of vitamin D [28, 29], and results osteoporosis in postmenopausal women with low calcium intakes [30]. Moreover, SNPs in genes encoding lipid proteins such as apolipoprotein C3 (APOC3) and apolipoprotein A1 (APOA1) conferred a higher risk of metabolic syndrome in subjects with a Western dietary pattern [31, 32]. Likewise, an increased risk of hypertension and CVD was observed with moderate and heavy coffee drinkers which was associated a genetic variation in the cytochrome P450 family 1 subfamily A member 2 (CYP1A2) gene [33, 34]. Additionally, studies using genetic risk scores (GRS) have been examined the cumulative effect of SNPs on diet interactions and susceptibility of diseases. Macronutrient is having the ability to modify the obesity GRS with greater values of adiposity [35]. Furthermore, obesity GRS interacted with the intake of sugar-sweetened beverages [36], and fried food

consumption [37] in relation to BMI and obesity in several cohort studies.

the obese phenotype that vary both within and across populations [43–46].

However, Hill et al. [47] given a concept positive energy balance which include increased intake of energy, decreased energy output and results deposition of energy. In this concept energy is represented as calories, if the intake of energy from diet is greater than the output then it cause (i) resting metabolic rate, (ii) absorption and metabolism of dietary nutrients, (iii) heat production or thermogenesis, and (iv) physical activity, a state of positive energy balance results to promote

Obesity is a chronic low-grade nutrition related inflammatory disorder and the important factor which is associated with a group of metabolic abnormalities/comorbidities commonly includes insulin resistance and hyperinsulinemia, hypertension, impaired glucose tolerance, noninsulin-dependent diabetes mellitus cardiovascular disease (CVD), type 2 diabetes, and a number of cancers [38, 39]. For the progression of obesity and the associated comorbidities are resultant of abnormal lifestyle leading habits, so here is the perfect place where nutrigenetics and nutrigenomics contribute their work to minimize obesity. Now the question which can be raised that is; whether all the individuals or populations are affected with obesity if obesogenic environment is provided; the answer is no, it is based on genetic variability and interaction with environmental factors according to Nakamura et al., [40], Nettleton et al., [41], Reddon et al., [42]. With reference to this the obesogenic environment comprises dietary nutrients, age, gender, ethnicity, duration of sleep, amount of physical activity, sedentary behavior, stress, smoking, alcohol consumption, use of medication, and depression. So it is an conclusive evidence that environmental factors is the primary cause for obesity vis gene-nutrientdisease interaction. If an individual having a good dietary habit with specific timing throughout the day along with physical exercise of at least 30 min daily, then he/ she can avoid such kind of metabolic disorder and its comorbidities. Nutrigenomics explain us the complex interactions of genome and its regulation differences among

*DOI: http://dx.doi.org/10.5772/intechopen.94602*

**4.1 Nutrigenomics and obesity**

*Nutrigenomics: An Interface of Gene-Diet-Disease Interaction DOI: http://dx.doi.org/10.5772/intechopen.94602*

*Mineral Deficiencies - Electrolyte Disturbances, Genes, Diet and Disease Interface*

**3. Nutrigenomic diseases and biomarkers**

fatty acid levels.

Mandard et al., [19], Kersten et al., [21] reported that fasted PPARα null mice mutant (lack of functional PPARα) suffers from a variety of metabolic defects, include hypothermia, hypoglycemia, hypoketonemia, and elevated plasma-free

Research regarding nutrigenomics is based on the principal of individuals nutrition-gene-disease interaction and how to protect the mankind from endangered non communicable diseases (NCDs) like cardiovascular diseases, obesity, diabetes, respiratory diseases, metabolic syndrome and cancers globally? Such type of NCDs are mediated by exposure of particular food components chronically, these are basically busy junk food eating lifestyle diseases of cities. These kinds of nutritional disorder are detected by biomarkers. It may be some disturbed lipid profiles to check the levels of cholesterol and/or triglycerides, increased blood pressure, or abnormal sensitivity of insulin as indicator of NCDs, like cardiovascular disease or metabolic syndrome. These biomarkers are mainly single proteins or metabolites or certain body functions that leads to be an detector for proteomics and metabolic changes in individuals body may be a causative agent's of a variety of chronic diseases which depends on the particular individuals genotype. The molecular aspects of individuals DNA damage can be diagnosed by a number of complementary ways are as follows: (i) damage to single bases (e.g. DNA adducts such as the addition of a hydroxyl radical to guanine caused by oxidative stress); (ii) abasic sites in the DNA sequence (measurable by use of the aldehyde-reactive probe); (iii) DNA strand breaks (commonly measured using the Comet assay); (iv) telomere shortening (measured by terminal restriction fragment length analysis, quantitative PCR or flow cytometry); (v) chromosome breakage or loss (usually measured using micronucleus cytome assays or metaphase chromosome analysis), and (vi) mitochondrial DNA damage (usually measured as deletions or base damage in the circular mitochondrial DNA sequence). These use of damaged DNAs as a biomarkers were recently validated at various levels based on the nutrient associated evidence (cross-sectional epidemiology and intervention studies) and disease (cross-sectional epidemiology and prospective cohort studies) as reported by Fenech, [8]. The micronucleus assay in cytokinesis-blocked lymphocytes is currently the best validated biomarker for nutritional genomic studies of DNA damage. In addition, a well validated nutrigenomics tool is transcriptomics, it includes the microarray assay to analyze the mRNA copies for all actively transcribed genes. The advantage of this technique is within same time it can analyze the expression level of transcripts, thousands of genes in a single assay. In peripheral blood cells, studies of gene-expression patterns have been shown to be specific for diseased states. Whereas, Martin et al., [22] noted that disease-specific gene-expression patterns in blood cells have been identified for breast tumors and leukemia was revealed by Valk et al., [23], and those patterns now used as biomarkers for the detection of

**12**

diseases.

**4. Gene-diet-disease interaction**

SNPs (Single nucleotide polymorphism) or SNVs (single nucleotide variants) are most widely acceptable markers now a days, responsible for genetic variation. Genotypic variations can be detected by SNPs or SNVs, and we can prescribe proper diet plan to avoid non communicable diseases (NCDs) like cardiovascular diseases,

obesity, diabetes and cancers. In this context, Ramos-Lopez et al., [24] revealed the sweet taste receptor (TAS1R2) related to taste perception and Ramos-Lopez et al., [25] depicted cluster of differentiation 36 (CD36), were associated with dyslipidemia in the peoples of Mexico, consume high amounts of carbohydrates and fats respectively. In addition, common variants of genes which regulate homocysteine metabolism, like methylene tetra hydrofolate reductase (MTHFR) and methionine synthase (MTR), are linked with the increased risk for breast cancer among individuals who intakes lower amount of folate, vitamin B6, and vitamin B12 [26]. The status of Vitamin D show polymorphism among the population and have the ability to modulate various metabolism in the organism [27]. Interestingly, the SNPs of the vitamin D receptor (VDR) gene, affect the availability of vitamin D [28, 29], and results osteoporosis in postmenopausal women with low calcium intakes [30]. Moreover, SNPs in genes encoding lipid proteins such as apolipoprotein C3 (APOC3) and apolipoprotein A1 (APOA1) conferred a higher risk of metabolic syndrome in subjects with a Western dietary pattern [31, 32]. Likewise, an increased risk of hypertension and CVD was observed with moderate and heavy coffee drinkers which was associated a genetic variation in the cytochrome P450 family 1 subfamily A member 2 (CYP1A2) gene [33, 34]. Additionally, studies using genetic risk scores (GRS) have been examined the cumulative effect of SNPs on diet interactions and susceptibility of diseases. Macronutrient is having the ability to modify the obesity GRS with greater values of adiposity [35]. Furthermore, obesity GRS interacted with the intake of sugar-sweetened beverages [36], and fried food consumption [37] in relation to BMI and obesity in several cohort studies.

#### **4.1 Nutrigenomics and obesity**

Obesity is a chronic low-grade nutrition related inflammatory disorder and the important factor which is associated with a group of metabolic abnormalities/comorbidities commonly includes insulin resistance and hyperinsulinemia, hypertension, impaired glucose tolerance, noninsulin-dependent diabetes mellitus cardiovascular disease (CVD), type 2 diabetes, and a number of cancers [38, 39]. For the progression of obesity and the associated comorbidities are resultant of abnormal lifestyle leading habits, so here is the perfect place where nutrigenetics and nutrigenomics contribute their work to minimize obesity. Now the question which can be raised that is; whether all the individuals or populations are affected with obesity if obesogenic environment is provided; the answer is no, it is based on genetic variability and interaction with environmental factors according to Nakamura et al., [40], Nettleton et al., [41], Reddon et al., [42]. With reference to this the obesogenic environment comprises dietary nutrients, age, gender, ethnicity, duration of sleep, amount of physical activity, sedentary behavior, stress, smoking, alcohol consumption, use of medication, and depression. So it is an conclusive evidence that environmental factors is the primary cause for obesity vis gene-nutrientdisease interaction. If an individual having a good dietary habit with specific timing throughout the day along with physical exercise of at least 30 min daily, then he/ she can avoid such kind of metabolic disorder and its comorbidities. Nutrigenomics explain us the complex interactions of genome and its regulation differences among the obese phenotype that vary both within and across populations [43–46].

However, Hill et al. [47] given a concept positive energy balance which include increased intake of energy, decreased energy output and results deposition of energy. In this concept energy is represented as calories, if the intake of energy from diet is greater than the output then it cause (i) resting metabolic rate, (ii) absorption and metabolism of dietary nutrients, (iii) heat production or thermogenesis, and (iv) physical activity, a state of positive energy balance results to promote

deposition of triacylglycerol within adipose tissue. Likely, in vice-versa condition, a state of negative energy balance results to promote lipolysis of triacylglycerol and mobilization of fatty acids from adipose tissue.

In addition, Stockard [48] described a fact that environment has an immense impact in obesity. 100 years ago he stated that the embryo and fetus develops in mother's womb can show a dramatic variation in the phenotype without changing the genomic constitution of the offspring while providing a moderate environmental constraint during specific periods of time in the development of the embryo. Along with this findings a new concept is explains the science working behind this i.e. epigenetic changes associated with obesity. Goldberg et al., [49] demonstrate the prenatal and early postnatal periods have a critical role in the developmental induction of obesity. Here, the epigenetics performed the lead role, during early nutritional environment of the fetus can increase the susceptibility to develop obesity in later life. Epigenetics can induce a heritable changes in gene expression without altering the gene sequences, it is basically the integral regulating and determining factor of when and where specific genes are expressed. The detail methylation pattern of epigenetics was depicted by Bird, [50], he noted that methylation at the 5´position of cytosine in DNA within a CpG (cytosine and guanine nucleotides linked by phosphate) dinucleotide is very common in mammalian genomes and leave a stable epigenetic mark which is transmitted through DNA replication and cell division. This de novo methylation is catalysed by DNA methyltransferases (Dnmts) 3a and 3b, and maintained through mitosis by gene-specific methylation of hemimethylated DNA by Dnmt1 [51].

Furthermore, different experiments done by various scientist describes versatile experiences related to obesity. Some evidential facts revealed by nutrigenomic scientists that if a new born with lower birth weight means the baby have reduced fat mass. Infants with lower birth weight who undergo early catch-up growth which is characterized by greater accumulation of fat relative to lean body mass have an increased risk of becoming obese in later life compared with those born at higher birth weights [52–54]. Similarly, in another experiment Singhal et al., [55], Singhal, [56] reported that infants born with lower birth weight having an catch-up growth were fed formula milk show increased risk of cardio-vascular disease in later life. A number of studies revealed that there is a greater chance of incidence of obesity in adults who were fed formula milk as compared to breast fed during infancy [57, 58], but exception are also there who were not fitted into this condition [59].

### **4.2 Nutrigenomics and cardiovascular disease (CVD)**

Cardiovascular disease (CVD), basically a heart disease affecting the heart and blood vessels includes arteries, capillaries, and veins. The CAD disease includes atherosclerotic, coronary and ischemic heart diseases, individuals carrying such diseases having plaques throughout the inner walls of arteries and leads to heart attacks. While age, gender and genomic constitution are an immutable risk factors for the occurrence of CVD, modifiable risk factors play a major role in the causation and progression of the disease. Some of the extra risk factors which is very common now a days due to busy and stressful life schedule like hypertension, hyperlipidemia, obesity, diabetes, atherosclerosis, thrombosis and smoking is a causative agent of CVD. Analyzing the complexity of the etiology of CVD outlined here Juma et al., [60] narrate some dietary recommendation for CVD prevention based on individuals genetic constitutions. In nutrigenomics diet is considered as environmental factors and which has a direct relationship with the development of chronic diseases, the CVD is not aloof of that. It's a well established fact proved by scientists that the personalized diet composition has a strong risk factor for development of CVD [61–64].

**15**

trations [69–73].

*Nutrigenomics: An Interface of Gene-Diet-Disease Interaction*

Obesity, itself is a curse in human population and is a leading risk factor to develop cardiovascular disease, diabetes mellitus and a number of cancers which is already discussed. In this context, to maintain the energy balance several polymorphic genes are involved to control the development of CVD in certain "favorable" or "unfavorable" condition [65]. Moreover, Lusis, [61] describes the role of atherosclerosis in the pathogenesis of CVD, it constitutes the key element and can be regarded as a complex combination of lipid transport and metabolism disorder with chronic inflammation. The levels of total cholesterol, LDL cholesterol, and triglycerides elevated permanently in the blood plasma which is causative agent for the development of atherosclerotic plagues, whereas increased levels of high density lipoprotein (HDL) i.e. cholesterol showed a protective role [65]. Genes responsible for encoding the apolipoproteins can be regulated by some signaling agents like hormones and enzymes but, it show differential sensitivity in population to develop cardiovascular diseases. In this context, individuals carrying the allele E4 of the apolipoprotein E gene show higher low-density lipoprotein-cholesterol (bad cholesterol) levels with increased intake of dietary fat as compared to those who carrying the E1, E2 andE3 alleles having equivalent amounts of dietary fat [66]. AG to A transition in the promoter of APOA1 gene is associated with increased HDL-cholesterol concentration but the results across studies are not consistent [67]. Whereas, Ordovas et al. [68] found that the allele A was associated with the decreased serum HDL levels. The genetic effect was reversed, however, in women who ate more polyunsaturated fatty acids (PUFA). In men, this type of fat effect was significant when alcohol consumption and tobacco smoking was considered in the analysis. Also specific polymorphism in genes encoding lipid transport proteins, their receptors, and lipid-processing enzymes and inflammation related proteins were shown to be associated with the characteristic changes in blood lipid concen-

To prevent or treat CVD an intense debate/discussion has been taking place for best dietary plan where the composition of macronutrients, the percentage of total fat along with different fatty acids presents are important [74–79]. Likewise, the source or origin of diet's composition is very essential, for e.g., individuals taken monounsaturated fatty acids from olive oils are different from monounsaturated fatty acids intake from meat and other foods of animal origin [79, 80]. Similarly, there is lots of controversy over the best origin and type (omega-6 and omega-3 series) of polyunsaturated fatty acids (PUFA) as reported by Jakobsen et al., [79] and Russo, [81] for prevention or treatment of CVD. In a same platform and same type of case study done by Shai et al., [82] and Sacks et al., [83] for controlling body weight and cardiovascular related risk factors where emphasis is given on to take high carbohydrate, low fat diet in comparison to high fat, low carbohydrate diet. In 1965, Keys et al, [84] in their study stated that it was an individual's "intrinsic characteristics" which controls the effect of diet in plasma concentrations of cholesterol, is an variable factor for person to person. Based on the facts, nutrition related counseling focused on weight reduction and normalization of lipid profiles through

Diabetes mellitus (DM), a group of metabolic diseases, results from defects in insulin secretion and insulin activity or both which is characterized by hyperglycemia. Georgoulis et al. [85] reported that due to this metabolic disease DM, various organs like blood vessels, heart and kidneys are dysfunction and/or failure, and now a days this disease is considered a global burden [86]. The International Diabetes Federation's recent estimates indicate that 8.3% of adults (382 million

diet, exercise, and medication for the prevention of CVD.

**4.3 Nutrigenomics and Diabetes mellitus**

*DOI: http://dx.doi.org/10.5772/intechopen.94602*

#### *Nutrigenomics: An Interface of Gene-Diet-Disease Interaction DOI: http://dx.doi.org/10.5772/intechopen.94602*

*Mineral Deficiencies - Electrolyte Disturbances, Genes, Diet and Disease Interface*

mobilization of fatty acids from adipose tissue.

of hemimethylated DNA by Dnmt1 [51].

deposition of triacylglycerol within adipose tissue. Likely, in vice-versa condition, a state of negative energy balance results to promote lipolysis of triacylglycerol and

In addition, Stockard [48] described a fact that environment has an immense impact in obesity. 100 years ago he stated that the embryo and fetus develops in mother's womb can show a dramatic variation in the phenotype without changing the genomic constitution of the offspring while providing a moderate environmental constraint during specific periods of time in the development of the embryo. Along with this findings a new concept is explains the science working behind this i.e. epigenetic changes associated with obesity. Goldberg et al., [49] demonstrate the prenatal and early postnatal periods have a critical role in the developmental induction of obesity. Here, the epigenetics performed the lead role, during early nutritional environment of the fetus can increase the susceptibility to develop obesity in later life. Epigenetics can induce a heritable changes in gene expression without altering the gene sequences, it is basically the integral regulating and determining factor of when and where specific genes are expressed. The detail methylation pattern of epigenetics was depicted by Bird, [50], he noted that methylation at the 5´position of cytosine in DNA within a CpG (cytosine and guanine nucleotides linked by phosphate) dinucleotide is very common in mammalian genomes and leave a stable epigenetic mark which is transmitted through DNA replication and cell division. This de novo methylation is catalysed by DNA methyltransferases (Dnmts) 3a and 3b, and maintained through mitosis by gene-specific methylation

Furthermore, different experiments done by various scientist describes versatile

experiences related to obesity. Some evidential facts revealed by nutrigenomic scientists that if a new born with lower birth weight means the baby have reduced fat mass. Infants with lower birth weight who undergo early catch-up growth which is characterized by greater accumulation of fat relative to lean body mass have an increased risk of becoming obese in later life compared with those born at higher birth weights [52–54]. Similarly, in another experiment Singhal et al., [55], Singhal, [56] reported that infants born with lower birth weight having an catch-up growth were fed formula milk show increased risk of cardio-vascular disease in later life. A number of studies revealed that there is a greater chance of incidence of obesity in adults who were fed formula milk as compared to breast fed during infancy [57, 58],

but exception are also there who were not fitted into this condition [59].

Cardiovascular disease (CVD), basically a heart disease affecting the heart and blood vessels includes arteries, capillaries, and veins. The CAD disease includes atherosclerotic, coronary and ischemic heart diseases, individuals carrying such diseases having plaques throughout the inner walls of arteries and leads to heart attacks. While age, gender and genomic constitution are an immutable risk factors for the occurrence of CVD, modifiable risk factors play a major role in the causation and progression of the disease. Some of the extra risk factors which is very common now a days due to busy and stressful life schedule like hypertension, hyperlipidemia, obesity, diabetes, atherosclerosis, thrombosis and smoking is a causative agent of CVD. Analyzing the complexity of the etiology of CVD outlined here Juma et al., [60] narrate some dietary recommendation for CVD prevention based on individuals genetic constitutions. In nutrigenomics diet is considered as environmental factors and which has a direct relationship with the development of chronic diseases, the CVD is not aloof of that. It's a well established fact proved by scientists that the personalized diet composition has a strong risk factor for development of CVD [61–64].

**4.2 Nutrigenomics and cardiovascular disease (CVD)**

**14**

Obesity, itself is a curse in human population and is a leading risk factor to develop cardiovascular disease, diabetes mellitus and a number of cancers which is already discussed. In this context, to maintain the energy balance several polymorphic genes are involved to control the development of CVD in certain "favorable" or "unfavorable" condition [65]. Moreover, Lusis, [61] describes the role of atherosclerosis in the pathogenesis of CVD, it constitutes the key element and can be regarded as a complex combination of lipid transport and metabolism disorder with chronic inflammation. The levels of total cholesterol, LDL cholesterol, and triglycerides elevated permanently in the blood plasma which is causative agent for the development of atherosclerotic plagues, whereas increased levels of high density lipoprotein (HDL) i.e. cholesterol showed a protective role [65]. Genes responsible for encoding the apolipoproteins can be regulated by some signaling agents like hormones and enzymes but, it show differential sensitivity in population to develop cardiovascular diseases. In this context, individuals carrying the allele E4 of the apolipoprotein E gene show higher low-density lipoprotein-cholesterol (bad cholesterol) levels with increased intake of dietary fat as compared to those who carrying the E1, E2 andE3 alleles having equivalent amounts of dietary fat [66]. AG to A transition in the promoter of APOA1 gene is associated with increased HDL-cholesterol concentration but the results across studies are not consistent [67]. Whereas, Ordovas et al. [68] found that the allele A was associated with the decreased serum HDL levels. The genetic effect was reversed, however, in women who ate more polyunsaturated fatty acids (PUFA). In men, this type of fat effect was significant when alcohol consumption and tobacco smoking was considered in the analysis. Also specific polymorphism in genes encoding lipid transport proteins, their receptors, and lipid-processing enzymes and inflammation related proteins were shown to be associated with the characteristic changes in blood lipid concentrations [69–73].

To prevent or treat CVD an intense debate/discussion has been taking place for best dietary plan where the composition of macronutrients, the percentage of total fat along with different fatty acids presents are important [74–79]. Likewise, the source or origin of diet's composition is very essential, for e.g., individuals taken monounsaturated fatty acids from olive oils are different from monounsaturated fatty acids intake from meat and other foods of animal origin [79, 80]. Similarly, there is lots of controversy over the best origin and type (omega-6 and omega-3 series) of polyunsaturated fatty acids (PUFA) as reported by Jakobsen et al., [79] and Russo, [81] for prevention or treatment of CVD. In a same platform and same type of case study done by Shai et al., [82] and Sacks et al., [83] for controlling body weight and cardiovascular related risk factors where emphasis is given on to take high carbohydrate, low fat diet in comparison to high fat, low carbohydrate diet. In 1965, Keys et al, [84] in their study stated that it was an individual's "intrinsic characteristics" which controls the effect of diet in plasma concentrations of cholesterol, is an variable factor for person to person. Based on the facts, nutrition related counseling focused on weight reduction and normalization of lipid profiles through diet, exercise, and medication for the prevention of CVD.

#### **4.3 Nutrigenomics and Diabetes mellitus**

Diabetes mellitus (DM), a group of metabolic diseases, results from defects in insulin secretion and insulin activity or both which is characterized by hyperglycemia. Georgoulis et al. [85] reported that due to this metabolic disease DM, various organs like blood vessels, heart and kidneys are dysfunction and/or failure, and now a days this disease is considered a global burden [86]. The International Diabetes Federation's recent estimates indicate that 8.3% of adults (382 million

individuals) have diabetes, and the number of individuals with this disease is expected to rise beyond 592 million in less than 25 years [86]. DM fall into two broad etiopathogenetic categories: type 1 and type 2 DM known as T1DM and T2DM, respectively. The epidemic global obesity noted by Prentice [87], he stated that virtually T2DM will be a major health issue in the world create a major drain on health budgets. Individual with obesity increases the risk of developing the disease DM by at least 10 fold as compared to normal one [88, 89]. In developing countries, peoples are shifted their lifestyle from traditional diets system to modernized fast food eating habit which include frequent consumption of red meat, refined carbohydrates and saturated fats is leads to obesity [90]. The insulin hormone, which is an important controller of glucose and fat metabolism is secreted from β-cells of pancreas. Irregular secretion insulin is observed in both the cases i.e. obesity and T2DM. Glucolipotoxicity is the results of high sugar and saturated fatty acid in diet on regular basis as suggested by Prentki et al. [91] and it negatively controls the secretion of insulin of from the β-cells, and results hyperglycemia and hyperlipidemia.

Flavonoids present in the diets include flavones, flavonols, flavanones, isoflavones, and anthocyanins. Various experimental studies suggested the protective role of polyphenols on glucose homeostasis mechanism, along with this some specific molecules like flavanols, luteolin, quercetin and others have a great impact on different steps of intracellular signalling pathways (insulin secretion, insulin signalling and glucose uptake, enhancing mitochondrial status, suppression of inflammatory cytokine production and reactive oxygen species (ROS)/reactive nitrogen). In addition to flavonoids, phenolic acids and tannins also have inhibiting property of the enzyme α-glucosidase and α-amylase which is responsible for carbohydrate digestion [92–97]. For instance, Song et al. [98] noted that consumption of apple or tea was associated inversely with T2DM risk. This is in accordance with the Health Professionals Follow-Up Studies also suggested that higher consumption of anthocyanins, particularly from pears, apples and blueberries, were inversely associated with T2DM [99].

Caffeic acid, chlorogenic acid (present in coffee) and ferulic acid (esterified to hemicelluloses in cereals) are the most common phenolic acids [96]. An inverse result with caffeinated, decaffeinated coffee and caffeine intake with T2DM in a dose-response manner (1–6 cups/day), compared with no or rare coffee consumption was observed in different epidemiological studies, which support the hypothesis i.e. habitual coffee consumption is associated with a substantially lower risk of T2DM [100, 101].

Resveratrol (trans-3,5,4′-trihydroxystilbene) is a natural phenol act as an phytoalexins, found in the skin of grapes, blueberries, mulberries, raspberries, peanutsand red wine, helps in reducing the complications of diabetes in many organs and tissues including liver and pancreatic β-cells and in different diabetic animal models [102]. It also improve the glucose homeostasis and give protection to pancreatic β-cells. It has an important role in insulin secretion and amelioration of metabolic disorders [103].

Whereas, Afzal et al., [104] depicted that lower vitamin D levels represent a risk factor for incident of T2DM in humans. However, the levels of hypovitamin D along with increased levels of parathyroid hormone (PTH) is an independent predictor of β-cell dysfunction, insulin receptor and glycemia [105]. Patients with T2DM with established hypovitaminosis improve glycaemia and insulin secretion by Vitamin D replenishment, not only through a direct action on pancreatic β-cell function but also via regulation of plasma calcium levels, which regulate insulin synthesis and secretion [106, 107].

**17**

*Nutrigenomics: An Interface of Gene-Diet-Disease Interaction*

Cancer is a multiple stages process in which gene expression, and protein and metabolite function begin to run aberrantly [108]. In today's genomic era, the cellular events which intercede the activation of carcinogenesis upon modulation by dietary factors, has led to flow of significant information which helped in understanding of this disease [109]. Cancer susceptibility may increase due to inherited mutations in genes. Gene diet interaction may increase the risk of developing cancer. Endogenous reactions, such as oxidations or from exogenous agents, sunlight exposure (skin cancer), such as tobacco smoke (lung cancer), aflatoxin (liver cancer), and relatively high doses of ionizing radiations (many types of cancers) [110] induces cancer. It is mandatory to have communication between nutrition, metabolism, and gene expression for upholding body homeostasis. Human genome and nutrition jointly interacts to do the same. Individual's health condition and susceptibility to disease may get affected due to this [111]. Nutrient regulates transcription factors at the molecular level which then modifies the gene expression (up or down), conse-

Diet is a blend of protective, carcinogenic, and mutagenic agents all together and are metabolized by the enzymes of biotransformation process. Risk of developing cancer can be modified through genetic polymorphisms that change protein expression or the function of these enzymes. Foods ingested by humans are proposed to contain more than 25,000 [113]. Role of different bioactive food ingredients in cancer pathogenesis has been studied and found that, among these, more than 500 types of bioactive food ingredients is proved to be possible predisposing agents. For carcinogens, diet is considered as a source (intrinsic or cooking-generated) present in certain foods or constituents acting in a protective manner (vitamins, antioxidants, detoxifying enzyme-activating substances, etc.) [114]. Carcinogen metabolism affecting polymorphisms may modify probability of contact between carcinogens and target cells, thus acting at the stage of cancer initiation [65]. In hormone dependent tumors such as breast, prostate, ovarian and endometrial cancers, influences of polymorphisms of gene encoding factors involved in hormonal regulation are most strongly manifested. Polymorphisms in sex hormone receptor genes comprising those encoding estrogen receptors, progesterone receptor, and androgen receptor have been shown to be associated with cancer risk modulation [65]. Hormonal regulation can be influenced on interaction with dietary factors. Obesity has strongly impact on hormonal status. Apparently, some food components, such as phytoestrogens are known to be processed by the path-

There are various examples of the effects of diet on cancer risk. High consumption of red meat increase the risk of colorectal cancer [66]. N-Acetyl transferase (NAT) exists in two forms: NAT1 and NAT2, it is a phase II metabolism enzyme. Several polymorphisms exist in NAT1 and NAT2, some of them are capable of slow, intermediate, or fast acetylations. Heterocyclic Aromatic amines found in heated products like cooked red meat get through acetylation by NAT. On cooking of muscle meat at high temperature, some amino acids may react with creatinine to generate heterocyclic aromatic amines (HAA). Acetylation activates HAA to reactive metabolites which bind DNA and cause cancers. This acetylation can only be performed by NAT2 fast acetylators. People who consumed relatively large quantities of red meat with NAT fast acetylator genotype had a higher risk of developing

Specific dietary irritants, such as salts and preservatives have been suggested as being carcinogens for gastric cancer [116]. C667T polymorphism in MTHFR gene

*DOI: http://dx.doi.org/10.5772/intechopen.94602*

quently to adjust the metabolic responses [112].

ways similar as sex hormones [115].

colon cancer in them [66].

**4.4 Nutrigenomics and cancer**
