Obesity%20used%20to%20be%20understood%20in%20fairly%20elementary%20behavioral%20terms:%20excess%20body%20weight%20resulting%20from%20eating%20too%20much%20and%20exercising%20too%20little,%20due%20in%20large%20part%20to%20a%20lack%20of%20willpower%20or%20self-restraint.%20But%20as%20people%20have%20increased%20their%20dieting%20and

1
Genotype Prevalence in the GenoTrim D.I.E.T.
Study Insights into Multi-Variant Obesigenics
from an Observational Study of Overweight
Subjects in The Netherlands Kenneth Blum,
PhD.1,2,4 Brian Meshkin, B.Sc.2 M
Martinez-Pons, Ph.D.3 Eric Braverman, M.D.4
1Department of Physiology Pharmacology, Wake
Forest University School Of Medicine 2
Department of Molecular Nutrition
Nutrigenomics, Salugen, Inc. San Diego,
California 3 Department Education, Brooklyn
College , CUNY, New York 4 Path Medical Research
Foundation, New York, NY
Discussion
Introduction
Results
Figures 3-6
Obesity used to be understood in fairly
elementary behavioral terms excess body weight
resulting from eating too much and exercising too
little, due in large part to a lack of willpower
or self-restraint. But as people have increased
their dieting and exercise, the rates of obesity
continue to rise as the combined prevalence of
overweight and obesity in the US has increased
from 46 of the adult populations (NHANES II,
1976 to 1980) to over 60 of the adult population
in NHANES III (1988-1994). In 1985, obesity was
recognized as a chronic medical disease with
serious health implications caused by a complex
set of factors. Obesity-related medical
conditions contribute to 300,000 deaths each
year, second only to smoking as a cause of
preventable death.1 Obesity has been established
as a major risk factor for hypertension,
cardiovascular disease, Type 2 diabetes, and some
cancers in both men and women. Obesity affects 58
million people across the nation and its
prevalence is increasing (source U.S. Census
Bureau). Approximately one-third of American
adults are estimated to be obese, and 60 are
overweight. In response to this rising epidemic,
the medical, food and fitness communities have
consistently told Americans to just make
behavioral modifications, such as diet and
exercise. As scientific advancements have
demonstrated in other neurological healthcare
conditions such as alcoholism, there are
important biological and genetic components that
limit the efficacy behavioral adjustments alone.
Sixteen years ago, Blum et al published
landmark research suggesting that another
prevalent healthcare condition which had been
traditionally characterized in behavioral terms
like obesity, namely alcoholism, also had a
hereditary or genetic component and that genetic
information could explain why such a condition
could be found to run in the family. Blums
research2, continued to explain how knowing this
important genetic information could then caution
certain genotypes to adjust their dietary intake
and environments to overcome this genetic
predisposition. In a recent study of 11,000
Americans, results suggested that more than 75
of obese Americans (n3,100) say they have
healthy eating habits. According to this survey,
40 percent of obese people also said they do
vigorous exercise at least three times per
week. In this survey by Thomson Medstat, a
Michigan-based healthcare research firm, obese
people reported similar behaviors in snacking,
reading nutritional labels, and eating out when
compared to normal weight people.3 Weight loss,
alone, is difficult, but sustainable weight loss
is also exceedingly difficult. Most people regain
as much as 2/3rds of weight lost within one year
and regain all within five years.
The Sweet Tooth Gene single nucleotide
polymorphism (SNP) was present in 38.09 of the
study subjects (n1,058) versus 29 of the
literature controls (n3,259). This difference
was significant (Z 8.393, p 0.0001) see
Figure 1. The Nervous Eating Gene SNP was
present in 64.18 of the study subjects (n1,058)
versus 61 of the literature controls (n284).
This difference was not statistically significant
(Z 0.755, p 0.23). The New Cell Gene SNP
was present in 69.85 of the study subjects
(n1,058) versus 54 of the literature controls
(n100). This difference was significant (Z
2.23, p 0.01) see Figure 2. The Obesity
Risk Gene SNP was present in 75.61 of the study
subjects (n1,058) versus 45.6 of the literature
controls (n206). This difference was
significant (Z 5.612, p 0.0001) see Figure
3. The Fat Regulator Gene SNP was present in
25.05 of the study subjects (n1,058) versus 14
of the literature controls (n2,245). This
difference was significant (Z17.398, p 0.001)
see Figure 4. The prevalence of genetic
combinations is also of interest see Figure 5
as 37.81 had 3 or more gene polymorphisms (PM),
73.91 had 2 or more gene PM. The most common
genotypes were Nervous Eating and New Cell Gene
PM (13.42), New Cell Gene PM (11.81), Sweet
Tooth, Nervous Eating and New Cell Gene PM
(10.4) and Nervous Eating Gen PM (7.84) see
Figure 6.
GenoTrim is the worlds first and only
DNA-customized nutritional solution for weight
and addresses the genetic factors influencing the
metabolism and hormones that impact weight. By
analyzing a panel of genes, GenoTrim is
DNA-customized to provide the consumer with a
nutritional supplement to assist in their weight
loss efforts. In the future, our goal as
scientists should be to provide the obese
individual a tailor made rather than a
one-size-fits-all solution. In this regard, we
maintain that this evidence underscores a need
for further nutrigenomic research to identify
various genes associated with obesity. And as
those genetic correlates are discovered, we
hypothesize using a multi-variant nutrigenomic
index for the purposes of customizing or
adjusting the formulation of nutritional
supplements will result in an improved and novel
approach to the diagnosis, stratification,
prognosis, and treatment of various healthcare
conditions.4 GenoTrim, the worlds first and
only DNA-customized nutritional solution for
weight management, was test launched in The
Netherlands in early 2006. The maker of
GenoTrim, Salugen, Inc. anticipates making the
product commercially available in the U.S. in Q4
2006. GenoTrim brings together a multivariate
genetic analysis of five genes addressing the
genetic factors influencing weight. These genes
include a serotonin receptor gene 5-HT2a-1438 AgtG
influencing appetite control, PPAR-Gamma
Pro(12)Ala polymorphism influencing fat cell
creation and metabolism, Leptin OB gene
influencing obesity risk, MTHFR C677T
polymorphism influencing folate (Vitamin B9)
metabolism and homocysteine, and Dopamine D2
Receptor Taq 1 Allele influencing sugar and
carbohydrate cravings. Based upon a genetic
profile derived from this in-depth genetic
analysis, a DNA-customized GenoTrim formula is
derived to address the genetic predisposition of
the subject, as a major contributing underlying
factor of their weight problems. The statistical
significance of this data suggests that these
genes are more prevalent in the obese and
overweight populations and underscores their
consideration when formulating a nutritional
solution to address weight problems. This
multi-variant analysis and DNA-customized
formulation process is a patented process of
Salugen, Inc., San Diego, CA USA.
Figure 3. Obesity Risk Gene Correlates with
Weight Problems
Figure 4. Fat Regulator Gene Correlates with
Weight Problems
Figures 1-2
Figure 1. Sweet Tooth Gene Correlates with Weight
Problems
 
Conclusion
This study is further evidence supporting the
role of these various genes and weight
management. Specifically, this first phase of
the D.I.E.T. Study makes a valuable scientific
contribution in identifying specific genotypes of
multi-variant genetic analyses that may be more
prevalent in obese or overweight populations and
thus should be considered as therapeutic targets
for complementary and alternative medicines, as
well as conventional therapies. With GenoTrim
being customized and targeted based upon these
various genotypes, GenoTrim is the first solution
to address genetic factors that statistically are
more common in an overweight and obese
population. As these genes have been documented
in their involvement in insulin sensitivity,
total serum homocysteine, aberrant craving
behaviors, anxiety and other healthcare
conditions, these genes also illuminate the
genetic roles of contributing co-morbidities to
the obesity epidemic and shed further light and
knowledge on the epidemic of obesigenics.
Figure 5. Multi-Gene Prevalence in the D.I.E.T.
Study
Methods
No. of Gene PM No. of Study Subjects Percentage
0 11 1.04
1 265 25.05
2 382 36.11
3 306 28.92
4 73 6.9
5 21 1.98
In this observational study, a total of 1,058
subjects were genotyped in the nutrigenomics
laboratory of Salugen, Inc. (San Diego, CA).
Each subject self-identified themselves as obese
or overweight by selecting GenoTrim as a
potential adjunct to their weight loss efforts.
Each subject was genotyped based upon the
following genetic mutations Sweet Tooth Gene
Dopamine D2 Receptor Gene Taq 1 Alelle (DRD2
A1), Nervous Eating Gene 5-Hydroxytrytamine 2A
-1438G/A promoter polymorphism (5-HT2a
-1438G/A), New Cell Gene Methylene
Tetrahydrofolate Reductase C677T polymorphism
(MTHFR C677T), Obesity Risk Gene Leptin
Genetic Polymorphism - OB1875 lt 208-bp alleles
(Leptin OB1875), and the Fat Regulator Gene
Peroxisome Proliferator-Activated Receptor-Gamma
Gene Pro12Ala polymorphism (PPAR-gamma Pro12Ala
Allele). The subjects are part of the Dutch
Investigation to Evaluate Treatments of
DNA-customized nutritional solutions for weight
management (D.I.E.T.) Study. The prevalence of
these genotypes was measured against literature
controls from independent, published clinical
studies involving the same genetic mutation in a
similar ethnic population. Statistical
significance was performed by a biostatistician
at Brooklyn College (NY) and determined using the
Z-test for two independent proportions (Kanji, G.
K. 100 statistical tests. 1997. Thousand Oaks,
California Sage Publications, Inc.).
Figure 2. New Cell Gene Correlates with Weight
Problems
References 1. Long-term pharmacotherapy in the
management of obesity. National Task Force on the
Prevention and Treatment of Obesity. JAMA, 1996
2761907-1915. 2. Stobbe, Mike. Survey Most
obese claim to eat healthy, Yahoo News,
http//news.yahoo.com/s/ap/20060802/ap_on_he_me/di
et_obesity_survey, August 15, 2006,
AtlantaAssociated Press reporting on Thomson
MedStat study. 3. Blum, K., Noble, E.P.,
Sheridan, P.J., Montgomery, A., Ritchie, T.,
Jagadeeswaran, P., Nogami, H., Briggs, A.H., and
Cohn, J.B., Allelic association of human dopamine
D2 receptor gene in alcoholism. Journal of the
American Medical Association 1990,263
2055-2060. 4. Blum K, Meshkin B, Downs BW. DNA
based customized nutraceutical gene therapy
utilizing a genoscore A hypothesized paradigm
shift of a novel approach to the diagnosis,
stratification, prognosis and treatment of
inflammatory process in the human. Med. Hypoth,
66, 1008, 2006.
Disclosures Both Kenneth Blum and Brian Meshkin
are stock holders and officers in Salugen, Inc.,
the makers of GenoTrim a DNA-customized
nutritional solution for weight management. For
more information on Salugen or GenoTrim, please
visit www.salugen.com and www.genotrim.com.