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

2. 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

3. 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

4. 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?

5. 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

6. 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

7. 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:
Editor In Chief –Journal of Nutrigenetics and Nutrigenomics (first publication January 2007)

8. 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

9. 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

10. 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

11. 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)

12. 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

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

14. 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.

15. 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.

16. 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

17. 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,

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

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

23. Thank you!!!