Know Your Genes: ACTN3 “The Sprint Gene”

This is the first post in an ongoing series called “Know Your Genes.” In it, we discuss one gene related to performance in some way. We talk about how it works in the body, the current research surrounding it, and how it is related to performance. I start each series with the same disclaimer:

“Caution: Taken alone, these single gene variants cannot determine your overall ability to perform the skill or have the physical trait that the gene encodes for. Abilities like running, jumping, and lifting are determined by many gene interactions and other external factors. Epigenetics also plays a role in that even with a propensity toward a certain trait or characteristic we can create epigenetic vertical shifts in our performance through the environment we place our bodies into.”

This week we look at ACTN3, the sprint gene.

What is it?

The ACTN3 gene produces the protein Alpha-actinin-3 (also known as alpha-actinic skeletal muscle isoform 3 or F-actin cross-linking protein). Alpha-actinin-3 belongs to a family of proteins called actin that perform many roles in the body. Actin comes either as a “globe shaped” protein or is linked together in a chain called filamentous actin which forms structures called microfibers . Actin performs many important functions like muscle contraction, cellular division, and cellular mobility.

Actin comes in 3 “isoforms” alpha, beta, and gamma. An isoform refers to proteins that have a similar function in the body, but slightly different structures. The beta and gamma forms of actin work in supporting the cytoskeleton (shapes and supports cells) and cell movement.

The isoform that we are interested in is the Alpha isoform which is found in both muscle and non-muscle cells. There are four total alpha-actinin genes in the body, ACTN 1-4. The two ACTN genes that function within skeletal muscle are ACTN2 and ACTN3. ACTN2 is found in the heart, all skeletal muscle in the body, and in the brain.

Finally, we get to ACTN3. ACTN3 is found in fast skeletal muscle fibers also called Type 2 muscle fibers or “fast-twitch” muscle fibers. To understand ACTN3’s use in muscle we have to understand some basic muscle physiology: the sarcomere.

The sarcomere is the basic structural unit of a muscle fiber. In the image of a sarcomere below, notice the areas called Z-bands. These bands from the borders of the sarcomere and provide structure and support across the sarcomere and connect to other sarcomeres to form muscle fibers. ACTN3 is found within these Z-bands and helps to provide support and also links actin “thin” filaments. The ACTN3 genes also play a role in muscle metabolism (more on that later).

From a genetic basis, people can carry one of three variants associated with athletic performance that either code for the amino acid  arginine or something called a stop codon. The types are RR, RX, or XX where R=Arginine X=Stop Codon. Those who have the XX form of the gene basically have a defunct gene that doesn’t code for any ACTN3.

Now that we know the role of ACTN3, let’s look at how it works in performance.

What does it do in relation to performance?

ACTN3 was first related to performance in a 2003 study that involving athletes from different sports and their genotypes. In the image below you can see the results from that study.

 

Image taken from: Yemima Berman, Kathryn N. North 

Notice that none of the Olympians in sprint sports and relatively few sprint athletes were found to have the XX genotype that codes for a defunct ACTN3 gene. Also of interest is the fact that many endurance athletes, including Olympic endurance athletes tested in the study, DID have the XX genotype.

This study started the discussion of whether carrying the RR or RX genotype was associated with an increased ability to perform power sports such as sprinting, power-lifting, or wrestling and if those who were carriers of XX were more prone to excel at endurance sports.

So the question is: Is the ACTN3 gene a good predictor of sports performance?

What does the science say?

Simple(ish) answer: No. Complex answer: Maybe

First off about 80% of people are carriers of either the RR or RX genotype. I don’t know about you, but 80% of the people that I know aren’t Olympic or collegiate level athletes.

Surprisingly, the people who are carriers of the XX genotype have a better idea of their performance ability based on their genotype. Around 18% of individuals are carriers of the XX genotype and based on previous studies very few elite level power athletes are carriers. Therefore, carrying the XX genotype MAY (big emphasis on may) mean that you could not reach an elite level as a power athlete. As always, there are documented cases that XX genotypes can perform at the elite level in power sport.

The more interesting question here, however, may be: How can people with the XX genotype not have some sort of visible trait that clearly shows they do not carry the gene for ACTN3?

Studies in mice that are deficient in the ACTN3 gene show that the activity of ACTN2 is increased in all muscle fibers making up for the deficiency of ACTN3. Interestingly, those mice also showed a shift in their muscle metabolism. Mice without ACTN3 had an increased capacity to oxidize fats, increased glycolysis (creates ATP which is used as energy in the body), and increased glycogen (the body’s storage form of glucose) within the muscle.

The longer we exercise, think endurance activities, the more glycogen our muscles use and the quicker the muscles will fatigue. At the same time, our bodies convert from using glycogen as the primary source of energy to fat which is done by oxidizing them to create energy. Hence, based on the mice study above, people with the XX genotype have an increase in muscle metabolism that favors endurance exercise.

What’s the verdict?

ACTN3 is associated with sports performance, though it does not cause a significant performance increase for either power or endurance. Those with the XX genotype less likely to perform at an elite level in power sports and also have a shift in muscle metabolism that favors endurance activity and may provide a slight beneficial advantage in endurance sports. The RR “speed and power” genotype is very common, especially among European populations and any increased ability in power sports in very small in nature.

Hope this helps. If you have any questions please feel free to email me at Ryan@prxperform.com

Also, if you liked this blog post, please check out my podcast.

Much love,

Ryan

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