Download PDF
Int J Sports Med 2012; 33(06): 419-420
DOI: 10.1055/s-0032-1311636
Editorial
© Georg Thieme Verlag KG Stuttgart · New York

Studies on Gene Polymorphisms in Sports Fancy Fashion or Important Field of Research?

H.-J. Appell Coriolano
,
J. A. Duarte
Further Information

Publication History

Publication Date:
29 May 2012 (online)

Also available at
    Permissions and Reprints

Abbreviations

ACTN3 : α-actinin-3 gene
ACE : angiotensin-converting enzyme gene
AMPD1 : monophosphate deaminase isoform 1 gene
CNB3 : β protein polypeptide 3 gene
COL6A1 : collagen type 6 gene
AQP-1 : aquaporin-1 gene
CK-MM : creatinkinase isoform MM gene

The influence of genetic vs. environmental factors on physical characteristics or sports performance has attracted the interest of researchers for many decades, resulting in a large number of twin studies. Beyond comparing only the phenotype of obviously identical genotypes, new strategies allowed the study of the influence of the genome on structural and functional human characteristics. There is no doubt that an orchestrated expression of the human genome is determinant to explain human individuality in sports performance.

Therefore, the area of genetics has received increasing interest in sports medicine over the last years. Meanwhile we understand, for instance, that exercise training does not simply result in temporary functional and structural adaptations, but also leads to profound up- or downregulations among several muscle genes [8]. A serious problem to be faced in the near future, or even already today, is an emerging tendency towards gene doping. This growing field led the Editors to launch a new section in the IJSM in 2007, dedicated to “Genetics & Molecular Biology”. Between 2007 and 2011 27 papers have been published in this section, among which 23 dealt with the association of gene polymorphisms with specific phenotypical characteristics. Gene polymorphisms may contribute to explaining the interindividual variability with respect to training responses and consequently different abilities for a specific physical performance.

Having selected from these 23 just the most recent papers published in the IJSM in 2010 and 2011 we should briefly outline which associations have been studied. Most studied polymorphisms were related to the ACTN3 gene [2] [5] [7] [12] [14] and linked to phenotypical characteristics like fat free body mass, muscle mass, muscle strength and power, muscle fatigue, or endurance/velocity performance. Other candidates were ACE associated with fat free mass, muscle mass and strength, and power performance [6] [7], AMPD1, CNB3 as well as COL6A1 associated with athletic performance [3] [9] [11], AQP-1 with loss of body fluid during exercise [10], and CK-MM with muscle damage [13].

Several of these studies associating physical characteristics with a special gene polymorphism frequently do not present coherent results. For instance, while the TT genotype of the GNB3 C825T polymorphism has a strong association with an elite endurance status in Israelis, this association did not exist anymore when pooling these subjects together with Spanish athletes [11]. Zempo et al. [14] studied the association of the ACTN3 R577X genotype with muscle mass in elderly Japanese women and found that this polymorphism positively influenced muscle mass. If one would accept that a higher muscle mass should allow for more strength development, this polymorphism should also be related to functional muscle parameters. However, this polymorphism was not found to be associated with muscle strength in elderly Brazilian women [7]. The same polymorphism was studied by Hanson et al. [5] in recreationally active young men and women; there were no associations with muscle performance phenotypes. Another study on ACTN3 R577X, as an example for the fragility of this kind of research design, found associations with endurance performance in Chinese female athletes, but not in their male counterparts [12]. Similarly discrepant results were obtained with Chinese elite sprint swimmers [2], where the frequency of the ACTN3 577 R allele was higher in female international athletes than in national level swimmers. Furthermore, pre-adolescent males with the RX or XX genotype showed greater improvement in sprint swimming that those carrying only the RR genotype [2].

Altogether these studies demonstrate widely incongruent results, which cannot be explained convincingly, and cause an entropy within the existing body of knowledge. Detecting polymorphisms per se is more or less a laboratory routine method, once the equipment has been mounted and is working; so technical problems should not account for the discrepant findings. There may, however, be several biasing factors within the research design; frequently encountered factors, for example, are the different ethnic background of the subjects or an insufficient sample size. Another pitfall in a kind of research design, which tries to associate different polymorphisms with physiological responses [2] might be the uncontrolled regression-to-the-mean artifact [1], suggesting strong associations, which in fact should be considered weak or even absent. There is also the difficulty of avoiding a type I (false positive) error in this exploratory or ‘data mining’ type of approach.

We strongly believe that the principal problem of these studies is linked to the conceptional background of the research. The rationale is almost always the same stressing some biological plausibility, i. e., to study whether there is an association between the A polymorphism and a B phenotype in a C specific population, somehow using a “look and see” strategy. Even if some authors are able to find significant associations, what kind of message do these data transport? Should we believe that exactly this or that polymorphism has to be held responsible for some kind of performance or that an individual carrying a special genotype should be looking forward to a great career as a sprinter? Certainly not, bearing in mind that any phenotype is a complex variable as the result of the interaction of multiple factors including genes and environment. With this kind of concept, researchers simply neglect other influences like epigenetic factors as well as gene-gene and gene-environmental interactions [4]. Indeed, if someone likes to attribute a phenotype to the influence of just one factor, such might be a small piece in the multicoloured mosaic of human physiology, but is far from understanding its complexity.

As a conclusion, we would like to encourage authors working in this field of research to thoroughly consider the presented aspects when planning future projects and writing their papers. On the other hand, we feel that adding further small isolated pieces of the large mosaic may not be helpful and does not improve our knowledge about the role of genetics in sports medicine.