by Dan Zhu
Common wisdom holds that a marathoner is unlikely to excel in a 100-meter race, and vice versa. While it is easy to imagine that genetic variation is a major source of such differences in athletic ability, identifying the actual genetic causes requires careful characterization of athletic traits and in-depth data analysis.
The ACE (angiotensin-converting enzyme) gene is one of the earliest and most widely studied genes in sports genetics (PMID 19696508). Everyone carries two copies of the ACE gene and each copy of it is either an I allele or a D allele. In the I (insertion) allele, there is an extra 287-base pair fragment of DNA that is absent in the D (deletion) allele.
Both alleles are common and each person has one of the three possible ACE genotypes — I/I, I/D or D/D.
A number of studies have found that the frequency of the I allele is higher in elite endurance athletes than in non-endurance athletes or non-athletes. For instance, in a study involving Caucasian athletes who completed either the 2000 or 2001 South African Ironman Triathlons, there was an excess of the I allele in the 100 fastest finishers as compared to the 100 slowest finishers or to non-athletic individuals (PMID 15292738). In another study of elite runners selected by the British Olympic Association as potential members of the national Olympic team, the I allele was present at a higher frequency in long-distance runners than in short-distance runners (PMID 10517757). Similar findings have also been reported in other sport disciplines, such as high-altitude mountaineering (PMID 18081503, PMID 9607758) and rowing (PMID 9737775).
There is a clear negative correlation between the I allele and the ACE protein activity in Caucasians. The ACE protein is a key regulator of blood pressure and many other aspects of cardiac and vascular physiology. However, the role of ACE in athletic performance is still not well understood.
Unlike genetic studies of common diseases involving large patient cohorts, association studies of athletic performance typically have small sample sizes and limited statistical power. This is also true for studies that demonstrated the association of ACE with endurance performance. This association should be considered preliminary because there have been studies that failed to show this association (PMID 19696508). It is also notable that this genetic association has been documented mostly in Caucasians, while data from African subjects did not show the same genetic effect (PMID 15950509).
ACE alone is not enough to ace it, because based on the preponderance of data from the scientific literature, it is likely that, on average, athletes with one or two I alleles have a better chance to achieve top performance in endurance sports than those with the D/D genotype. However, this genetic effect should be kept in perspective because athletic performance is a complex trait and ACE is only one of the many contributing genetic factors. ACE is among a very small number of genes that have so far been studied for association with athletic performance; also the whole field of sports genetics is still at a rudimentary stage. Therefore, we cannot predict a person’s athletic potential based on his or her ACE genotype alone. Indeed, in all the studies mentioned above, there were individuals with the DD genotype who were elite endurance athletes.
Athletic performance is a perfect example of gene-environment interaction. In order to develop sporting prowess, even the most talented athletes need to train consistently and properly. The ACE genotypes have only a slight physiological effect that is largely unnoticed in non-athletes, but I allele carriers are likely to gain more benefit from endurance training than non-carriers (PMID 19696508); this enhanced training response may explain why athletes carrying the I allele have better endurance performance. In other words, both good genes and hard work are necessary ingredients for successful athletic achievement.