Race and Sports: ACE I/D Issues

[Guest guest]

Here are a few abstracts from another lengthy article on the Race and

Performance issue. Note that the URL below will probably wrap around onto

several lines in your email letters, so be very careful to copy the full

address into your browser when you try to go to this article.

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<http://journals.bmn.com/journals/list/browse?uid=TEM.etd00537_10432760_v0011i

10_00000310 & rendertype=abstract>

The ACE I/D Polymorphism and Human Physical Performance

R. Woods, Steve E. Humphries and Hugh E. Montgomery

Trends in Endocrinology and Metabolism 2000, 11:416-420

Abstract

The D allele of the angiotensin-converting enzyme (ACE) I/D polymorphism is

associated with elevated levels of serum and tissue ACE, increased production

of the vasopressor angiotensin II and a reduction in the half-life of the

vasodilator bradykinin. Several cardiac and renal conditions appear to have a

worse prognosis in subjects homozygous for the D allele, whereas the I allele

has been associated with enhanced endurance performance in elite distance

runners, rowers and mountaineers. The nature of the gene-envirnoment

interaction between ACE I/D polymorphisms and physical training, an overview

of recent findings and a discussion of possible underlying mechanisms is the

subject of this review.......

Other workers have failed to find an association between the I allele and

elite endurance performance 7–9 . The common denominator among these studies

has been the selection of athletes from mixed sporting disciplines, albeit

all with an element of endurance. Population association studies test whether

a genetic marker (the polymorphism/allele) occurs more frequently in

specified groups than in controls, a significant association suggesting that

the allele being studied is itself responsible, or is at least in the locus,

or that this allele is in linkage disequilibrium with the 'real' locus.

Several confounding factors, including subtle phenotypic differences, make

comparison between investigations difficult. What exactly is an elite

endurance athlete? Olympic runners and Australian national rowers might

represent a slightly different endurance phenotype from the skiers and

swimmers forming part of the cohorts in the studies with negative findings

7–9 . Certainly, if one combines different sporting disciplines, one combines

several slightly different phenotypes and confuses the issue being evaluated.

The positive findings regarding the ACE genotype and endurance have compared

individuals within one sporting discipline with a control group, and as such,

are more acceptable. Eliminating variables that might influence the 'elite

athlete' phenotype (as opposed to the 'endurance' phenotype) might require

the examination of the gene frequency within a sporting discipline that has

an increasing element of endurance. This increases phenotypic homogeneity,

focuses on the effect of the ACE genotype with regard to endurance within a

discipline and has previously produced positive findings.......

Findings relating endurance performance to the ACE genotype have always been

either in military recruits or in elite athletes and mountaineers, where a

prolonged period of training and, therefore, gene-environment interaction,

has taken place. In determining factors that might enhance endurance

performance, we should ideally examine the change in a parameter, with

training as an environmental stimulus. If attempting to investigate a gene–

environment interaction (in this case the interaction of the ACE gene I/D

polymorphism with exercise training), then it is crucial that as many other

environmental factors as possible are kept constant. British military

recruits are particularly suitable for these studies because they are all

sleeping in the same location, eating the same diet, sleeping the same hours

and exercising to identical supervised targets at identical times. They are

also often of one sex, from a very narrow age band and from a similar racial

background.......

Are there Factors other than Cardiorespiratory Fitness that Might Influence

the ACE Genotype Response to Training?

The findings of Rankinen and colleagues from a well-designed longitudinal

study, with strictly supervised training and a large number of subjects,

showed no evidence to support a hypothesis that the enhanced endurance

characteristics conferred by the ACE I allele result from improvements in

cardiorespiratory fitness. However, endurance performance can vary greatly

among individuals with an equal Vo2 max (Refs 18, 19), suggesting that other

factors might play a significant role........

Summary and Future Directions

The I allele does seem to be associated with enhanced endurance performance,

probably via a local muscle effect rather than a central cardiorespiratory

mechanism. Future research might clarify the exact relationship between the

ACE I/D polymorphism and ACE expression in skeletal muscle and the

interaction of this with training on muscle fibre type and size,

mitochondrial and capillary density and substrate utilization. If future work

demonstrates that low ACE levels mediate the benefit of the I allele and

confirm that this improves muscle efficiency, this may allow us to manipulate

situations where whole body oxygen and substrate delivery are compromised,

such as in heart failure or malignant disease. If we develop new insights

into improving cellular efficiency, then in conditions such as myocardial or

cerebral infarction we might be able to develop new therapeutic strategies or

increase indications for existing drugs to counteract the sudden reduction in

cellular delivery of metabolic substrates and oxygen associated with these

states. Consistent with this hypothesis, ACE inhibition improves myocardial

cell survival in the face of ischaemia and patient survival in cases of

cardiac dysfunction.....

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Dr Mel C Siff

Denver, USA

Supertraining/