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.
What 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 earnest.
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 temptation.
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 and behaviors.
Our intensive 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 more information,
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 drugs
· 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 950-988-7550.
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 tomorrow's meal.
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 associated SNPs.
Don’t despair! 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 population. Typical 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: regular 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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