Development and Validation of a Weight Management Genetic Test Shyam Ramakrishnan, PhD New Technology

Why weight management panel Why weight management panel? Basic Paradigm for a Genetic Predisposition to Obesity Energy Partitioning Favoring Fat Accretion Adipogenesis Obesity Overweight Energy Intake Genetic Predisposition Energy Expenditure

What constitutes Weight Management Gene Panel? Nutrigenetic approach How your genes affect, for example, the metabolism of the food you ingest Consists of a set of genes and their polymorphisms

Purpose of the Weight Management Gene Panel Can we help guide our customer to an optimal combination of diet and exercise to achieve personal weight management goals?

Topics Genetic Test Development process Selection criteria and description of genes ‘Bucketing’ genes into diet preference categories Preliminary validation of the Weight Management Genetic Test

Topics Genetic Test Development process Selection criteria and description of genes ‘Bucketing’ genes into diet preference categories Preliminary validation of the Weight Management Genetic Test

Drivers Behind the Weight Management Gene Panel Based on the work of Dr. Louis Perusse (Laval University) Recognized as one of the world’s top authorities in the field of genetics and obesity One of 8 authors of the Obesity Gene Map Rankinen T, Zuberi A, Chagnon YC, Weisnagel SJ, Argyropoulos G, Walts B, Perusse L, Bouchard C. The human obesity gene map: the 2005 update. Obesity 2006;14:529-644. Editor In Chief –Journal of Nutrigenetics and Nutrigenomics (first publication January 2007)

Topics Genetic Test Development process Selection criteria and description of genes ‘Bucketing’ genes into diet preference categories Preliminary validation of the Weight Management Genetic Test

Obesity Gene Map Database 100+ Gene Variants from Obesity Gene Map Database YES GeneOb review of literature evidence for obesity linkage 16 gene variants associated with obesity identified Plausible biologic effect and variant functionality YES NO-Reject FABP2, PPARG ADRB2 and ADRB3 4 genes and their variants selected Can diet or exercise Positively/negatively influence body weight, body fat, or metabolism according to genotype as shown by clinical studies? YES

Topics Genetic Test Development process Selection criteria and description of genes ‘Bucketing’ genes into diet preference categories Preliminary validation of the Weight Management Genetic Test

Bringing It All Together… Exercise Diet Genotypes. Low-fat Low-carb Bal-cal Regular Exercise All genotypes not in “Less responsive/vigorous” category below (12%) FABP2 54Thr/* AND PPARG Pro12Pro 5% PPARG 12Ala/* AND FABP2 54Thr/* OR ADRB2 27Glu/* AND/OR PPARG 12Ala/* All genotypes not meeting low CHO or Low Fat 2% Vigorous Exercise Less Responsive ADRB3 Trp64Arg ADRB2 Arg16Gly 89% 34% 40% 14% Total 39% LOW FAT 45% LOW CARB 16% BAL CAL Note: Percentages in each recommendation “bucket” represent expected frequencies from the Caucasian population in the Quebec Family Study. (* indicates that the second allele can be either Ala or Thr)

Topics Genetic Test Development process Selection criteria and description of genes ‘Bucketing’ genes into diet preference categories Preliminary validation of the Weight Management Genetic Test

Christopher D. Gardner, PhD Director of Nutrition Studies at Stanford Prevention Research Center; Associate Professor of Medicine at Stanford University and CHP/PCOR Associate

Preliminary Validation of the Weight Management Test-Results Demonstrated that individuals following diets matched to their genotype, as measured by the genetic test, showed that statistically significant greater weight loss and other benefits at all time points (2 mos, 6 mos and 12 mos) when compared to individuals on diets not matched to their genotype.

4 diets—3 popular and substantially different diets and 1 diet based on national guidelines—representing a spectrum of carbohydrate intake: Atkins8 (very low in carbohydrate), Zone9 (low in carbohydrate), LEARN18 (Lifestyle, Exercise, Attitudes, Relationships, and Nutrition; low in fat, high in carbohydrate, based on national guidelines), and Ornish19 (very high in carbohydrate). The Atkins group aimed for 20 g/d or less of carbohydrate for “induction” (usually 2-3 months) and 50 g/d or less of carbohydrate for the subsequent “ongoing weight loss” phase.

Total energy intake was not different among diet groups at baseline or any subsequent time point (P.40 for all). However, relative to baseline, there was a significant mean decrease in reported energy intake at all postrandomization time points

In this study of overweight and obese premenopausal women, those assigned to follow the Atkins diet had more weight loss and more favorable outcomes for metabolic effects at 1 year than women assigned to the Zone, Ornish, or LEARN diets. Concerns about adverse metabolic effects of the Atkins diet were not substantiated within the 12-month study period. Retention at 12 months was 88%, 77%, 76%, and 78% for the Atkins, Zone, LEARN, and Ornish groups, respectively,

Summary of the results (~6 kg) (~2.1 kg)

Conclusion The study, for the first time, showed the possibility of appropriately selected gene/gene polymorphisms guiding selection of the macronutrient composition

Thank you!!!