Index -- WPGYN Newsletter -- Volume 10, Issue 1, January 2013
How do Genes Influence Obesity?
Can you blame your weight on
genetic factors? Studies
of family members, twins, and adoptees offer indirect scientific
evidence that a portion of the variation in weight among adults is due
to genetic factors. Variants in some genes may influence behaviors,
like a drive to overeat, and others may influence metabolism, like a
tendency to store energy as fat. See
the article entitled “Genetics loads the gun and lifestyle pulls the
trigger” for more detailed information.
Studies also show that our
environment or lifestyle can influence whether certain genes are turned
on or turned off. For
example, as we become overweight and store fat, we become more insulin
resistant, setting up a viscious cycle of a tendency to develop type 2
diabetes and put on even more weight.
Most obesity results from complex interactions among
multiple genes and environmental factors that remain poorly understood
(multifactorial obesity.) It
is clear that the current epidemic in this country has only become a
problem in the past 50 years, even though the genes have not changed
much during that time.
Other Factors Influence Weight Gain?
Dr. David Kessler, author of
“The End of Overeating” believes that the food industry is largely to
blame for the increase in overweight individuals and high obesity rates
in recent times. He
points out that the food industry designs hyper-palatable combinations
of sugar, fat and salt that rewire our brains, driving us to seek out
more and more of those rewarding products.
Although the food industry
helped create this problem, the good news is that we are not helpless
and weight loss is possible. The
brain neural pathways that create the desire to overeat can’t easily be
wiped out, but they can be managed.
Strategies for Successful Weight Loss
When it comes to weight loss,
there's no shortage of diet plans. In fact, you’ve probably
tried a number of them. Hundreds of fad diets,
weight-loss programs and outright scams promise quick and easy weight
loss. The first few weeks always go
so well, but they don’t work for the long term.
The key to successful weight loss is a commitment to
making permanent changes in your diet and exercise habits.
How do you make those permanent
changes? If you have not been able to succeed on your own, an organized
and professional program will improve your success.
Consider following these six strategies for
weight-loss success adapted from the Mayo Clinic Diet.
1. Make a commitment
The commitment to permanent weight loss will
require time, effort, and focused attention.
You must be willing to make permanent changes in
your lifestyle. If
multiple stresses are taking you in multiple directions, this may not
be the right time for you to be successful.
Make sure that you're ready to make permanent
changes and that you do so for the right reasons.
When you’re ready, set a start date, and start in
2. Find your inner motivation
No one else can make you lose
weight. No one else
can want it for you more than you want it for yourself.
Make a list of what's important to you to help stay
motivated and focused, whether it's to look good at next year’s
Christmas party or to get your cholesterol down. Then find ways to
remind yourself of your personal motivations during moments of
It also helps to have support —
of the right kind. Pick people to support you who will encourage you in
positive ways, and offer accountability.
If you prefer to keep your weight-loss plans
private, be accountable to yourself by having regular weigh-ins and
recording your diet and exercise progress in a journal.
3. Set realistic goals
It may seem obvious to set realistic weight-loss goals, usually losing 1 to 2 pounds (0.5 to 1 kilogram) a week is about right, though it may go more quickly at the beginning. Decide on an outcome goal, like “Lose 20 pounds”, but also set process goals like “Exercise 30 min 5 days a week”. Process goals will help you change your habits which is a key to successful weight loss.
4. Enjoy healthier foods
Adopting a new eating style
that promotes weight loss must include lowering your total calorie
intake. But decreasing calories need not mean giving up taste,
satisfaction or even ease of meal preparation. One way you can lower
your calorie intake is by eating more plant-based foods — fruits,
vegetables and whole grains. Strive for variety to help you achieve
your goals without giving up taste or nutrition.
5. Get active, stay active
The key to weight loss is
burning more calories than you consume.
While you can lose weight without exercise, exercise
plus calorie restriction can help give you the weight-loss edge. .
Exercise also offers numerous health benefits, including boosting your
mood, strengthening your cardiovascular system and reducing your blood
pressure. Exercise can also help in maintaining weight loss. Studies
show that people who maintain their weight loss over the long term get
regular physical activity.
6. Change your perspective
It's not enough to eat healthy foods
and exercise for only a few weeks or even months if you want long-term,
successful weight loss. These habits must become a way of life. Work
out a strategy to gradually change habits and attitudes that have
sabotaged your past efforts. You
likely will have an occasional setback. But instead of giving up
entirely after a setback, simply start fresh the next day. Remember
that you're planning to change your life. It won't happen all at once.
Stick to your healthy lifestyle and the results will be worth it.
Because 2/3rds of our patients need an action plan in this important aspect of health care, we have developed a program with all of the ingredients to bring about long-term success. Quick fix dieting doesn’t work, but long term changes that address your brain chemistry and alter your relationship with food will result in success!
In our weight
loss program, you’ll eat foods that you like, learn to gain conscious
control of your eating and gradually gain the awareness you need to
decrease your calories, lose weight and most importantly maintain new habits
weight management program includes 12 weekly visits with options of
affordable, continuing follow-up. You will be under the care of a
registered dietitian, Joanne
Donovan, with 20 years of experience and a registered Nurse
Practitioner, Barbara Dehn, who is able to do
the necessary medical monitoring, including prescription of medications
if indicated. For
Have you ever thought about
testing your DNA using a direct to consumer kit?
Would the benefits justify the expense? If you’ve been on the
fence, this may be a good time to act since 23andMe just lowered their
price from $299 to $99. I
just sent off my saliva sample.
I’m not expecting earth-shaking
insights into my health. In
fact, a detailed family history is probably more reliable in predicting
your risk of disease than the data you will get from 23andMe. However, some information
could be very useful, such as:
· How you will respond to certain
· Whether or not you carry
certain recessive genes, especially important if you or a close family
member is planning a pregnancy
· What are your ancestral links,
with possible clues to new cousins
· The ability to upload your DNA
results to a wonderful and free website: GEDmatch.com, with tools for
genetic genealogy research .
But when it comes to complex
diseases, like heart disease, diabetes, obesity or cancer, there are so
many different sites involved on so many different genes, that the
probabilities or predispositions you learn from 23andMe do not make any
diseases a certainty or assure you that you won’t develop a given
disease. On the
other hand, knowing your risk is above that of the general population
might influence you to take extra steps for prevention or do extra
screening for early diagnosis.
To understand the limitations of this and other genetic testing, it helps to review what our genome is all about. It’s hard to conceive that we each have over 3 billion base pairs in our genome (our 23 chromosomes). That means limitless opportunities for differences between one person and the next. Wow! About 2% of these base pairs make up 20,000-25,000 protein-coding genes which determine how our bodies function. A change in one base pair of the DNA code is called a single-nucleotide polymorphism (SNP). Some changes cause definite disease, like cystic fibrosis. Many changes are poorly understood and are known to have complex interactions with other genes, with the environment, and with disease.
You can think of the
genome as a set of 23 books that contain all the information necessary
to make our bodies function. Each
book represents a chromosome. Just
like a book contains many chapters, each chromosome contains many genes. The chapters are composed
of sentences which are formed from words which are formed from letters. Each letter is a DNA base
pair made up of only 4 letters—A, T, C, and G.
The words in the genes are sequences of 3 DNA base
pairs, each of which codes for one of 20 amino acids.
Substitutions of one letter for another, e.g. CAT
vs. CAG, causes different amino acids to be substituted into proteins. We all have millions of
such variations which helps to explain the huge variability in
characteristics from one human to another.
23andMe tests for about 1
million SNPs known to associated with physical characteristics,
heritage, or disease, but that is only a small percentage of the total
number of DNA base pairs. In
contrast to testing for SNPs, some companies are beginning to offer
whole exxome sequencing which reads the DNA letter by letter for all
25,000 protein-coding genes, or whole genome sequencing which reads
letter by letter for all 3 billion base pairs.
Why is 23andMe
offering such a deal? One
of their goals is to collect a huge DNA data-base that can be used for
research purposes, for example by pharmaceutical companies. In my opinion, that is a
good thing and will ultimately lead to more personalized medicine for
all of us. You can
order your DNA testing kit at www.23andMe.com.
If you need help interpreting the results, please
make an appointment with Dr. Sutherland for a consultation at
The genes that
your mom and dad passed on to you determined your eye color, your
height and many of your personality traits and there's not much that
you can do about those. Of the 20,000 to
25,000 genes that each of us carries we all have some that put us at
risk of disease but not all these diseases are inescapable. It's ironic
that the diseases that kill most of us, though influenced by our genes,
are mostly avoidable. And
the leading ones such as heart disease, cancer and stroke are strongly
associated with obesity and smoking.
As discussed in
the last article, there are dozens of genes that are related to obesity
and nearly everyone on the planet has at least a few of them. Not a
single one of these genes will cause a person to become obese unless
that individual also takes in more calories than he or she uses up. On
the other hand, some genes make our fat-accumulating mechanism
extremely efficient while at the same time making it hard to burn off
fat. In the thousands of years before food supplies became stable,
holding on to fat was an advantage that helped humans to survive
periods of food scarcity. That survival trait has become a deadly
disadvantage in a world where fewer and fewer humans worry about
Rarely, a clear pattern of
inherited obesity within a family is caused by a specific variant of a
single gene (monogenic obesity.) A
gene linked to obesity called the FTO gene has been identified. If the FTO gene is not
working properly, the risk of obesity is increased because carriers
choose to eat too many high fat and high calorie foods. There seems to be a fat-satiety disconnect. If you
carry double copies of this obesity gene (one from each of your
parents) your risk of becoming obese is 2.5 times higher than a
non-carrier. Seventeen percent of the general population has double
obesity genes, and another 40 percent have a single copy. But you can’t blame an
extra 50 pounds on the obesity gene.
In a European study, people with one copy weighed on
average 1.2 kilograms (2.6 lb) more than people with no copies. Carriers
of two copies weighed 3 kilograms (6.6 lb) more. Studies show the FTO
variant has frequencies of 45% in the West/Central Europeans, 52% in Yorubans (West African natives) and 14%
in Chinese/Japanese. By
the way, the 23andMe test does not include the FTO variant most
directly associated with BMI, but they report your results at another SNP on the
FTO gene that is closely linked to it as well as several other obesity
People with the FTO gene variation are not destined
for obesity. Your genetics
will only activate if you give it the right environment to do so – like
eating a high fat diet and being sedentary. Lifestyle plays an important
role in influencing susceptibility to the FTO obesity gene.
With today’s aging
of baby boomers, the incidence of patients with Alzheimer’s and the
families who care for them is going up.
Some 5.4 million Americans have Alzheimer’s, and the
numbers are expected to swell. With
the explosion of knowledge in genomics, should we be doing more to
identify genetic predispositions for this devastating disease?
When it comes to
the genetics of Alzheimer’s, it is important to recognize the
difference between early onset (< age 65) and late onset
(>age 65) Alzheimer’s. The
early onset forms only comprise about 6–7% of all cases of AD. About 60% of these
patients have an autosomal dominant disease with a high risk of passing
it on to family members. Three genes have been implicated in early
onset AD: APP,
presenilin 1 (PSEN1), and presenilin
2 (PSEN2). Carriers
of these genes have a 95 – 100% chance that they will develop
Alzheimer’s. If you
have a family member, especially a first degree relative (parent or
sibling) who developed Alzheimers at age <65, you might want to
make an appointment with a genetic counselor to discuss the pros and
cons of testing that person for these genes.
I recommend Lily Servais, MS,
LCGC, the genetic counselor at El Camino Hospital, who you can contact
by phone (650-988-8361) or email (Lily_Servais@elcaminohospital.org.)
If your close relative is positive, you would have a
50% chance of inheriting the gene.
When it comes to
late-onset AD, the role of genetics is much less clear.
The apolipoprotein E (APOE) gene is the major
susceptibility gene for late-onset forms. APOE4 is present in about 50%
of patients with Alzheimer’s disease and approximately 14% of the total
estimates suggest a 2- to 3-fold increased risk for Alzheimers if you
carry one copy of the APOE4 gene, and a 2 to 10 fold risk if you carry
2 copies of the APOE4 gene. But
even a 10 fold risk does not mean you are destined to get Alzheimers. Things you can do to
reduce your risk of dementia include:
exercise, healthy diet, mental stimulation, quality sleep, stress
management, and an active social life.
· Type 2 Diabetes
The genetics of type 2 diabetes
is complex with multiple genes making only small contributions to risk. The exception in the MODY
gene which is rare but is highly likely to result in diabetes at a
young age (20s or 30s)and which is inherited as an autosomal dominant. That means there is a 50%
chance that close (first degree) relatives will inherit it. In general, if a close
relative is diagnosed with diabetes before the age of 50, there is a 1
in 7 chance you will get diabetes.
If diagnosed after 50, the risk goes down to 1 in 13. Some of the “genetic” risk
may also relate to shared lifestyle habits—like high processed
carbohydrate diets and lack of exercise.
It has been well shown that improving weight, eating
habits and exercise, can reduce your risk of diabetes even if you have
a family history.
This is a similar
story. There are a
few well-known but rather rare genes, like the BRCA genes for breast
cancer or the HNPCC or Lynch syndrome genes for colon cancer, that significantly increase
one’s risk. The
23andMe test is very limited in its testing of cancer predisposition
genes. For example,
when it comes to the BRCA genes, they only test 3 SNPs common in
Ashkenazi Jewish women. A "low
risk" result on their test doesn't mean that you don't carry some other
serious mutation elsewhere on the BRCA gene. As with other
diseases with a genetic tendency, a family history and a genetic
predisposition of cancer is certainly not a destiny.
Exercise, a healthy diet with lots of fruits,
vegetables and grains, stress management, and maintaining a normal
weight can all go a long way towards cancer prevention.
There has been some confusion as to whether both Dr. Litwin and Dr. Sutherland are retiring. Rest assured that I, Dr. Sutherland, have no plans to retire anytime soon. I am happy to take over the care of Dr. Litwin's patients, providing the same high quality of care that has always distinguished the Women Physicians Medical Group.
Information on this website is for educational and reference purposes only and should not be interpreted as specific medical advice.
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Women Physicians Gyn Medical Group