One copy of a particular version of the ACE gene has been found more often in elite endurance athletes, and every climber tested to date who has ascended over 8,000m. Your FitnessGenes result tells you whether you carry this endurance version, the alternative power/strength version or both.


The ACE gene was the first to be linked to athletic performance and has been one of the most extensively studied genes in sport.  It comes in two forms: a long version (the I allele) and a short version (the D allele). Increased endurance potential has been strongly linked with having two copies of the long version (II).  In contrast, having two copies of the short version (DD) has been associated with power/strength, although this link does not appear as strong.

The ACE gene is part of a complex hormonal system which affects numerous tissues in our bodies and is important in regulating our blood pressure and fluid balance among many other roles.  The fact this system affects multiple tissues makes it difficult to pinpoint the exact effects that the different genotypes are having, but there are trends in the research that help us make our recommendations.

While the effect of the ACE gene seems more pronounced in elite level athletes than in untrained or non-highly trained individuals, the scientific research still gives clues as to how individuals with different ACE genotypes may perform or respond to different types of exercise or training strategies.

Global population distribution:

Source: 1000 Genome Project. Global averages for both sexes

ACE: II

30%

ACE: ID

46%

ACE: DD

24%

More about ACE

IMPACT OF THE DIFFERENT ACE GENOTYPES

There are two different versions of the ACE gene that we analyse for you: the I, or Insertion version (which can be described as the long version due to the insertion of extra DNA) and the D, or Deletion version (which is the short version due to the absence of this extra DNA).

Both versions produce active ACE protein, but they differ in the levels produced. Those who carry two copies of the D allele have been shown to produce more ACE protein than those who carry two copies of the I allele. People who have one copy of each allele (ID) have intermediate levels of ACE.

ACE stands for ‘Angiotensin I-Converting Enzyme’ and the protein produced by this gene is part of the renin-angiotensin system. This is a complex hormonal system that is important in regulating blood pressure and fluid balance. The ACE protein is responsible for the production of the hormone angiotensin II which causes blood vessels to constrict, encourages fluid retention and, as a result, increases blood pressure. ACE also interacts with and breaks down a protein called bradykinin which has the opposite effect to angiotensin II (relaxes blood vessels, encourages fluid loss from the body and decreases blood pressure).

Therefore it has been proposed that people with the DD and ID genotypes may have a slightly increased risk of high blood pressure than those with the II genotype. However, results from studies looking at the association of the ACE genotype and blood pressure have not always been consistent. While the ACE genotype does seem to contribute, it is unlikely that a single gene will have a definite effect due to the presence of other genetic and environmental factors.

The power of the I allele in elite-level endurance

Studies have shown that the frequency of the I allele is greater in elite endurance athletes when compared to the general population. This has been shown in a variety of different sporting disciplines including rowing, cycling, long-distance running, swimming (> 400 m) and triathlons. Interestingly the I allele is also overrepresented in elite mountaineers. In one study of 15 climbers who had ascended beyond 8000 metres without oxygen, none had two copies of the D allele.

Studies have also found associations of the D allele with strength and have shown it to be overrepresented in elite power/strength athletes. These include everything from American, Russian, British, European and Commonwealth swimmers (≤ 400 m) to Greek sprinters, Japanese wrestlers and Portuguese and Spanish power athletes.

However, there are some studies which contradict these results while other studies have found no association between ACE genotype and athletic performance. Measuring the associations between genes and physical traits is difficult and a lack of consistency between how these studies are carried out, differences in the kind of athletes and numbers studied leads to researchers reporting different results. Despite this, the research still points to a strong association of the I allele with elite endurance athletes and slightly weaker but still significant association of the D allele with elite power/strength athletes.

Interestingly, and similar to the ACTN3 gene, the ACE genotype has not been shown to be associated with elite endurance performance in elite African long-distance runners, suggesting alternative genetic factors may be at play in these populations.

Impact on muscle & lean body mass

Carrying a copy of the I allele is positively associated with the percentage of slow-twitch muscle fibres an individual possesses. In untrained individuals it was shown that II individuals had a greater percentage of slow-twitch muscle fibres compared to both ID and DD individuals. In fact there appeared to be a trend between a decrease in slow-twitch muscle fibres and increase in fast-twitch fibres (type IIx) according to genotype, in the order II > ID > DD.

One study showed that the DD genotype was associated with higher lean body mass and bodyweight in men while muscle volume of the quadriceps was greater for both male and females compared to the II and ID genotypes. Another study also showed that individuals with different ACE genotypes differed in their muscle biomechanical properties and the results could even be used to predict an individual’s ACE genotype.

Angiotensin II, the product of ACE activity, is known to affect skeletal muscle hypertrophy in rats and therefore it has been suggested that the ACE genotype, in particular the D allele, could potentially be linked with muscle growth. The D allele has also been associated with hypertrophy of the heart in humans and it could be possible that it has a similar effect in skeletal muscles. So far studies in humans measuring their response to resistance training have not shown significant increases in muscle size to be unequivocally associated with ACE genotype though.

Finally, II individuals may be more susceptible to muscle damage as serum creatine kinase (CK) levels were shown to increase more in these individuals in response to eccentric exercise. DD individuals had the smallest increase in CK and ID individuals were intermediate between the two homozygous groups.

Response to strength exercise and training

Your ACE genotype could potentially affect how you respond to different training intensities (amount of weight) and volumes (number of reps and sets).

One particular study showed that people with different ACE genotypes respond differently to different training volumes. All genotypes responded to resistance training and showed significant increases in strength. However, II individuals were shown to respond better in terms of using multiple sets and higher reps (12-15), whereas DD individuals did not differ greatly in strength increases when using a single set or multiple sets. Therefore it has been proposed that II genotypes may respond better to lower intensity, higher volume training while DD genotypes might respond to higher intensity, lower volume training.

Some studies have also suggested that DD individuals or D allele carriers have greater strength or bigger increases in strength in response to training. One showed that D allele carriers had greater strength gains in response to isometric training then II’s. Further studies have shown that baseline strength was associated with ACE genotype (with DD carriers being stronger than ID, and ID carriers stronger than II). However other studies have failed to find any association between ACE genotype and either baseline strength or response to strength training or have even presented conflicting results!

Differences in the muscle properties might also exist between the genotypes. I allele carriers significantly improved the duration they could perform repetitive elbow flexions with a 15 kg weight over a 10 week general physical training program, whereas DD individuals did not. The researchers noted that these differences were not due to changes in the strength or size of the arm muscles and that it was more likely due to improvements in the endurance capacity of the muscles used. This is supported by other studies which show that II individuals improve the efficiency of muscles trained much more than ID and DD individuals. Two further studies also add support to the idea that II individuals may have either more efficient muscles or are more efficient in supplying their muscles with the necessary metabolites they need to function. II individuals might also have better peripheral tissue oxygenation and lower lactate concentration during exercise.

Finally, in some of the studies described and in others, only small non-significant differences before training or in response to exercise were seen and this suggests that the ACE genotype does not have a very large effect in physically inactive or non-highly trained people.

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