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Genetics and high-fat diets: how a DNA test can help you make better decisions

Welcome to The Weekly Gene, a blog series brought to you by Helix that introduces a different human gene each week. We’ll share important facts, relevant research, and how these genes might be related to certain conditions and traits. It’s a great way to build your DNA vocabulary, learn more about the code that makes all of us unique, and find a path to the genetic insights that are important to you.
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Many people know that high-fat diets can increase a person’s risk of obesity and heart disease, but fewer may know that genetics can influence how dietary fat affects the body. This means that two people who eat the same high-fat diet might gain weight at a significantly different rate due to slight changes in their DNA. When you’re working on a healthier lifestyle, knowing how your DNA interacts with your diet can be valuable information.
Stated plainly, you need to eat some fat. A common misconception is that all fats are bad, but in reality the body relies on some dietary fats for survival. The term “fat” refers to a large family of molecules that share some defining chemical properties. As a whole, fats are used for many functions in the body ranging from insulation to hormone signaling and the storing of nutrients. At a molecular level, fats are important components of the membranes that help compartmentalize a cell—a key feature that allowed primitive lifeforms to evolve into complex organisms like human beings.

To ensure that every tissue has the fat it needs, our bodies have developed an elaborate fat transportation mechanism in which cholesterol, proteins, and fat are packaged into structures known as lipoproteins. Depending on the proteins present, lipoproteins can either take cholesterol and fat to the liver where they will be broken down (known as high density lipoproteins—HDL), or they can transport them to other parts of the body for storage (known as low density lipoproteins—LDL). While fats are needed for normal body function, too much dietary fat can result in severe health conditions. Excessive fat in the bloodstream can become embedded within blood vessel walls and ultimately cause heart attacks. More immediate effects of high dietary fats can include an increase in fat storage, leading to elevated body weight and body mass index (BMI). For these reasons, it is usually beneficial to break down fat and cholesterol rather than storing it.

You need to eat some fat

The body’s ability to break down fat is partly determined by genetic factors. One gene with a significant impact on fat is Apolipoprotein A2 (APOA2), one of the main proteins in HDL packages. Studies1,2 have shown that changing the DNA sequence coding for APOA2 at a single location from a thymine (T) to a cytosine (C) is associated with increased waist circumference and an elevated BMI in individuals with a high fat diet. This single base pair change might decrease production of the APOA2 protein, but it’s not yet clear what molecular role APOA2 proteins play in a person’s BMI.

  1. Corella, D., et al. “The -256T>C Polymorphism in the Apolipoprotein A-II Gene Promoter Is Associated with Body Mass Index and Food Intake in the Genetics of Lipid Lowering Drugs and Diet Network Study.” Clinical Chemistry, vol. 53, no. 6, 2007, pp. 1144–1152., doi:10.1373/clinchem.2006.084863.
  2. Zaki, Moushira Erfan, Khalda Sayed Amr, and Mohamed Abdel-Hamid. “ APOA2 Polymorphism in Relation to Obesity and Lipid Metabolism.” Cholesterol 2013 (2013): 289481. PMC. Web. 11 Oct. 2017.