What Will It Take to Build an Expert Group of Nutrigenomic Practitioners?

BACKGROUND: The past two decades have seen exponential growth in the number of genetic testing companies, but only a small percentage of these tests are being sold through health care professionals (HCPs). As each new genetic testing company appears, it is becoming more difficult for the practitioner and consumer to evaluate the credibility of the claims being made and the value of the tests being offered. SUMMARY: HCPs appear to have minimal nutrigenomics knowledge and little confidence in choosing and interpreting nutrigenetic tests. To remedy this, HCPs need access to credible education, professional support, networking, career development, mentorship, and a regulated testing environment. This will enable them to evaluate the credibility of genetic tests and testing companies, provide genetic results in context, and apply appropriate clinical translation. Key Message: In order to establish an expert group of nutrigenomic practitioners, collaboration is required between educational institutions, professional organizations, and genetic testing companies. This will provide the necessary support, skills, and knowledge to ensure that the best value is extracted from nutrigenetic tests in an ethical and responsible manner.

Personalized Nutrition: Translating the Science of NutriGenomics Into Practice: Proceedings From the 2018 American College of Nutrition Meeting.

Adverse reactions to foods and adverse drug reactions are inherent in product defects, medication errors, and differences in individual drug exposure. Pharmacogenetics is the study of genetic causes of individual variations in drug response and pharmacogenomics more broadly involves genome-wide analysis of the genetic determinants of drug efficacy and toxicity. The similarity of nutritional genomics and pharmacogenomics stems from the innate goal to identify genetic variants associated with metabolism and disease. Thus, nutrigenomics can be thought of as encompassing gene-diet interactions involving diverse compounds that are present in even the simplest foods. The advances in the knowledge base of the complex interactions among genotype, diet, lifestyle, and environment is the cornerstone that continues to elicit changes in current medical practice to ultimately yield personalized nutrition recommendations for health and risk assessment. This information could be used to understand how foods and dietary supplements uniquely affect the health of individuals and, hence, wellness. The individual's gut microbiota is not only paramount but pivotal in embracing the multiple-functional relationships with complex metabolic mechanisms involved in maintaining cellular homeostasis. The genetic revolution has ushered in an exciting era, one in which many new opportunities are expected for nutrition professionals with expertise in nutritional genomics. The American College of Nutrition's conference focused on "Personalized Nutrition: Translating the Science of NutriGenomics Into Practice" was designed to help to provide the education needed for the professional engagement of providers in the personalized medicine era.

A Novel Approach to the Nutrigenetics and Nutrigenomics of Obesity and Weight Management.

Nutrigenetics and nutrigenomics, as well as diet and exercise, play an important role in the development and treatment of obesity and its comorbidities. If an individual's susceptibility to becoming obese and their responsiveness to weight loss interventions are to be understood, then it needs to be addressed at a molecular and metabolic level, including genetic interaction. This review proposes a three-pillar approach to more fully comprehend the complexity of diet-gene interactions in obesity. Peroxisomal proliferating-activated receptor gamma (PPARG) and mitochondrial uncoupling protein-1 (UCP-1) are explored in detail. Illustrating how an understanding of nutritional biochemistry, nutrigenomics, and nutrigenetics may be the key to understanding differences observed in the obese phenotype that vary both within and across populations.

Interleukin-6 gene polymorphisms, dietary fat intake, obesity and serum lipid concentrations in black and white South African women.

This study investigated interactions between dietary fat intake and IL-6 polymorphisms on obesity and serum lipids in black and white South African (SA) women. Normal-weight and obese, black and white women underwent measurements of body composition, serum lipids and dietary fat intake, and were genotyped for the IL-6 -174 G>C, IVS3 +281 G>T and IVS4 +869 A>G polymorphisms. In black women the IVS4 +869 G allele was associated with greater adiposity, and with increasing dietary fat intake adiposity increased in the IVS3 +281 GT+GG and IVS4 +869 AA or AG genotypes. In white women, with increasing omega-3 (n-3) intake and decreasing n-6:n-3 ratio, body mass index (BMI) decreased in those with the -174 C allele, IVS3 +281 T allele and IVS4 +869 AG genotype. In the white women, those with the IVS3 +281 T allele had lower triglycerides. Further, with increasing n-3 polyunsaturated fatty acid (PUFA); triglyceride and total cholesterol:high-density lipoprotein cholesterol (T-C:HDL-C) ratio decreased in those with the -174 C allele. In black women, with increasing total fat intake, triglycerides and T-C:HDL-C ratio increased in those with the IVS4 +869 G allele. This study is the first to show that dietary fat intake modulates the relationship between the IL-6 -174 G>C, IVS3 +281 G>T and IVS4 +869 A>G polymorphisms on obesity and serum lipids in black and white SA women.

The relationship between dietary fatty acids and inflammatory genes on the obese phenotype and serum lipids.

Obesity, a chronic low-grade inflammatory condition is associated with the development of many comorbidities including dyslipidemia. This review examines interactions between single nucleotide polymorphisms (SNP) in the inflammatory genes tumor necrosis alpha (TNFA) and interleukin-6 (IL-6) and dietary fatty acids, and their relationship with obesity and serum lipid levels. In summary, dietary fatty acids, in particular saturated fatty acids and the omega-3 and omega-6 polyunsaturated fatty acids, impact the expression of the cytokine genes TNFA and IL-6, and alter TNFα and IL-6 production. In addition, sequence variants in these genes have also been shown to alter their gene expression and plasma levels, and are associated with obesity, measures of adiposity and serum lipid concentrations. When interactions between dietary fatty acids and TNFA and IL-6 SNPs on obesity and serum lipid were analyzed, both the quantity and quality of dietary fatty acids modulated the relationship between TNFA and IL-6 SNPs on obesity and serum lipid profiles, thereby impacting the association between phenotype and genotype. Researching these diet-gene interactions more extensively, and understanding the role of ethnicity as a confounder in these relationships, may contribute to a better understanding of the inter-individual variability in the obese phenotype.

The -308 G/A polymorphism of the tumour necrosis factor-α gene modifies the association between saturated fat intake and serum total cholesterol levels in white South African women.

This study explored interactions between dietary fat intake and the tumour necrosis factor-α gene (TNFA) -308 G/A polymorphism on serum lipids in white South African (SA) women. Normal-weight (N = 88) and obese (N = 60) white SA women underwent measurements of body composition, fat distribution, fasting serum lipids, glucose, insulin concentrations and dietary intake. Subjects were genotyped for the functional -308 G/A polymorphism within the TNFA gene. There were no significant differences in the genotype or allele frequencies between groups, and no significant genotype associations were found for body fatness or distribution, or serum lipid concentrations. However, there was a significant interaction effect between dietary saturated fat (SFA) intake (%E) and TNFA -308 genotypes on serum total cholesterol concentrations (P = 0.047). With increasing SFA intake (%E), serum total cholesterol levels decreased for the GG genotype and increased for the GA plus AA genotypes. The TNFA -308 G/A polymorphism appears to modify the relationship between dietary fat intake and serum total cholesterol concentrations in white SA women.

Tumor necrosis factor-alpha gene -308 G/A polymorphism modulates the relationship between dietary fat intake, serum lipids, and obesity risk in black South African women.

The prevalence of obesity and related disease risk is high in black South African (SA) women, possibly influenced by the dietary transition associated with urbanization. This study explored interactions between dietary fat intake and the tumor necrosis factor-alpha (TNFA) -308 G/A polymorphism on obesity, insulin resistance, and serum lipid concentrations in urbanized black SA women. Normal-weight (n = 105) and obese (n = 118) women underwent measurements of body composition, fat distribution, fasting serum lipids, glucose and insulin concentrations, and dietary intake. Participants were genotyped for the functional TNFA -308 G/A polymorphism. The genotype or allele frequency of the TNFA -308 G/A polymorphism did not differ between the BMI groups. However, when dietary fat intake was 30% of total energy intake [percentage energy (%E)], the odds of being obese with the TNFA GA+AA genotype was only 12% of that with GG, but increasing intake of dietary fat (%E) was associated with a significantly faster rate of increase in obesity risk in women with the TNFA GA+AA genotype compared with those with the GG genotype (P = 0.036). There were significant diet-gene interactions between alpha-linolenic acid (%E) and the total cholesterol:HDL-cholesterol ratio (P = 0.036), and PUFA (%E) and LDL cholesterol levels (P = 0.026), with participants with the A allele being more responsive to changes in relative fat intake. The TNFA -308 G/A polymorphism modified the relationship between dietary fat intake, obesity risk, and serum lipid concentrations in black SA women.

Dual-energy X-ray absorptiometry and anthropometric estimates of visceral fat in Black and White South African Women.

Visceral adipose tissue (VAT) is associated with increased risk for cardiovascular disease, and therefore, accurate methods to estimate VAT have been investigated. Computerized tomography (CT) is the gold standard measure of VAT, but its use is limited. We therefore compared waist measures and two dual-energy X-ray absorptiometry (DXA) methods (Ley and Lunar) that quantify abdominal regions of interest (ROIs) to CT-derived VAT in 166 black and 143 white South African women. Anthropometry, DXA ROI, and VAT (CT at L4-L5) were measured. Black women were younger (P < 0.001), shorter (P < 0.001), and had higher body fat (P < 0.05) than white women. There were no ethnic differences in waist (89.7 +/- 18.2 cm vs. 90.1 +/- 15.6 cm), waist:height ratio (WHtR, 0.56 +/- 0.12 vs. 0.54 +/- 0.09), or DXA ROI (Ley: 2.2 +/- 1.5 vs. 2.1 +/- 1.4; Lunar: 2.3 +/- 1.4 vs. 2.3 +/- 1.5), but black women had less VAT, after adjusting for age, height, weight, and fat mass (76 +/- 34 cm(2) vs. 98 +/- 35 cm(2); P < 0.001). Ley ROI and Lunar ROI were correlated in black (r = 0.983) and white (r = 0.988) women. VAT correlated with DXA ROI (Ley: r = 0.729 and r = 0.838, P < 0.01; Lunar: r = 0.739 and r = 0.847, P < 0.01) in black and white women, but with increasing ROI android fatness, black women had less VAT. Similarly, VAT was associated with waist (r = 0.732 and r = 0.836, P < 0.01) and WHtR (r = 0.721 and r = 0.824, P < 0.01) in black and white women. In conclusion, although DXA-derived ROIs correlate well with VAT as measured by CT, they are no better than waist or WHtR. Neither DXA nor anthropometric measures are able to accurately distinguish between high and low levels of VAT between population groups.

Association between the 4 bp proinsulin gene insertion polymorphism (IVS-69) and body composition in black South African women.

The objective of the study was to examine the association between a functional 4 bp proinsulin gene insertion polymorphism (IVS-69), fasting insulin concentrations, and body composition in black South African women. Body composition, body fat distribution, fasting glucose and insulin concentrations, and IVS-69 genotype were measured in 115 normal-weight (BMI<25 kg/m2) and 138 obese (BMI>or=30 kg/m2) premenopausal women. The frequency of the insertion allele was significantly higher in the class 2 obese (BMI>or=35 kg/m2) compared with the normal-weight group (P=0.029). Obese subjects with the insertion allele had greater fat mass (42.3+/-0.9 vs. 38.9+/-0.9 kg, P=0.034) and fat-free soft tissue mass (47.4+/-0.6 vs. 45.1+/-0.6 kg, P=0.014), and more abdominal subcutaneous adipose tissue (SAT, 595+/-17 vs. 531+/-17 cm2, P=0.025) but not visceral fat (P=0.739), than obese homozygotes for the wild-type allele. Only SAT was greater in normal-weight subjects with the insertion allele (P=0.048). There were no differences in fasting insulin or glucose levels between subjects with the insertion allele or homozygotes for the wild-type allele in the normal-weight or obese groups. In conclusion, the 4 bp proinsulin gene insertion allele is associated with extreme obesity, reflected by greater fat-free soft tissue mass and fat mass, particularly SAT, in obese black South African women.

Determinants of insulin-resistant phenotypes in normal-weight and obese Black African women.

OBJECTIVE: Subsets of metabolically "healthy obese" and "at-risk" normal-weight individuals have been previously identified. The aim of this study was to explore the determinants of these phenotypes in black South African (SA) women. METHODS AND PROCEDURES: From a total of 103 normal-weight (BMI or= 30 kg/m(2)) black SA women, body composition, fat distribution, blood pressure, fasting glucose levels, insulin resistance, and lipid profiles were measured. Questionnaires relating to family history, physical activity energy expenditure (PAEE), and socio-demographic variables were administered. The subjects were classified as insulin sensitive or insulin resistant according to the homeostasis model assessment of insulin resistance (HOMA-IR) (>or=1.95 insulin resistant). RESULTS: Our study showed that 22% of the normal-weight women were insulin resistant and 38% of the obese women were insulin sensitive. Increased visceral adipose tissue (VAT) (P=0.001) and decreased VAT/leg fat mass (P