Investigations of environmental and genetic influences on East African distance running success

The primary objective of these experiments was to assess the environmental and genetic contributors to east African running success. Elite Ethiopian and Kenyan athletes, as well as matched controls, consented to participate in the current series of experiments by completing a questionnaire on their ethnic and environmental background, and by providing a buccal swab for analysis of novel and existing candidate genes for human performance. The aim of the first two studies presented in this thesis (Chapters three and four) was to compare the demographic characteristics of elite Ethiopian and Kenyan athletes with those of their source populations. This was to assess the validity of reports linking their success to altitude inhabitation and having ran long distances to school each day during childhood. In both experiments, it was found that the elite athletes were clustered in regions of high altitude, proximal to the Rift Valley. However, in Ethiopia, non-endurance athletes were also found to cluster in these areas, so the link between altitude and elite athlete status may not simply be as a result of haematological adaptations conferring benefit in endurance performance. It was also found that elite athletes had travelled farther to school each day as children, and more of them had done so by running. In addition, the athletes displayed a distinct ethnicity relative to the general population. The associative nature of the experiments did not allow causality to be assigned to any one factor, but the results highlight the importance of environmental factors in the determination of elite east African athlete status. The aim of Chapter five was to compare the frequency of mtDNA haplogroups between elite Ethiopian athletes with the general Ethiopian population. Elite Ethiopian athletes were not a genetically distinct group, as defined by their mtDNA. This does not support hypotheses that east African athletes arise from a limited genetic isolate. Chapter six aimed to compare the mtDNA haplogroup frequency between elite Kenyan athletes and the Kenyan control group. Kenya also displays a wide degree of mtDNA variation, but displays a different haplogroup distribution from Ethiopia, with a higher frequency of typically African 'L' haplogroups (Ethiopia = 54 %, Kenya = 90 %). Findings of ethnic variation in mtDNA haplogroup frequency meant that influences of population stratification could not be ruled out. The experiment in Chapter seven compared the frequency of Y chromosome haplogroups in elite Ethiopian athletes with that of the general Ethiopian population. Y chromosomal DNA is inherited solely down the paternal line and is confined solely to males. Y chromosome variants have been associated with a diverse range of phenotypes in health and disease, making the Y chromosome a viable candidate gene for physical performance in males. Similar to mtDNA, the non-recombinant pattern of inheritance makes the Y chromosome useful in population genetics to determine the ancestry of individuals or populations. Certain Y chromosome haplogroups were associated with elite Ethiopian athlete status. Athletes showed an excess of E3*, a lower frequency of E3b, and a tendency toward an excess of K(xP) haplogroups relative to controls. Although no influence of region or ethnicity was found on haplogroup distribution, effects of population stratification could not be ruled out. These results suggest that Y chromosome variation may influence elite Ethiopian athlete status. Perhaps the most studied variant of the candidate genes for human performance is the ACE I/D polymorphism. A number of studies have associated the ACE I allele with endurance performance, while the D allele has been associated with power type performance. The experiment in Chapter eight aimed to compare ACE I/D genotype frequencies between elite Ethiopian and Kenyan athletes and their source populations. It was found that male Ethiopian marathon runners showed an excess of II genotypes relative to controls. However, this association was not replicated in 5-10 km Ethiopian runners, or in Kenyan distance runners. It is unlikely that the I/D polymorphism is functional in influencing variation in the ACE phenotype. Other variants in the ACE gene are more strongly associated with serum ACE levels in African populations, where levels of linkage disequilibrium differ from Caucasian populations. For this reason, A22982G was genotyped in elite athletes and controls. This variant showed a stronger association with serum ACE levels than the I/D polymorphism in the Kenyan control group. However, there was no association between A22982G genotype and elite athlete status in either Ethiopian or Kenyan athletes. These results do not support a role for ACE gene variation in the determination of elite East African athlete status. (Abstract shortened by ProQuest.)