Genes affecting fitness and stamina
An individual’s fitness depends on the aerobic capacity regarding aerobic-anaerobic and fitness strengthening sports. By this the maximum oxygen uptake is meant which can be used by organism under physical loading. The aerobic capacity with its strong genetic background contributes to the athletes’ performance in endurance sports. The genetic predisposition of aerobic fitness is primarily based on the examination of those genes which can be related to cardio respiratory condition as well as energy metabolism of muscles.
Fitness is closely related to mitochondrial metabolic activity and the development of mitochondrial gene-expression (genexpress). Enzymes play an important part in energy metabolism. The functioning of mitochondrion is controlled by peroxisome proliferator-activated receptor (PPAR). PPARð controls genes which are functioning in carbohydrate metabolism and by affecting insulin sensitivity they modify the sugar uptake of skeleton muscle fibre. One SNP in PPARð gene (+ 294T/C) results in increased PPARð level, thus relating fitness to performance. Observing the functioning of mitochondrion and endurance the PPARð coactivator-1α (PPARGCIA) is the polymorphism of Gly-482Ser. It is present in different proportions in elite long distance runners and rowers. Nuclear respiratory factors (NRF1 and NRF2) coordinate the relevant gene expression in mitochondrial biogenesis. They play a crucial role in the interaction between the nucleus and mitochondrion. NRF2 is present, for example, in the promoter region of cytochrome protein nuclear gene which is the member of all the five electro-transport chains. There are biding sites in genes which encode mitochondrial import proteins and heme biosynthesis proteins while controlling the nuclear elements and mitochondrial gene-expression of respiratory chain. A/G polymorphism observed in NRF2 gene can also explain the endurance capacity variance of individuals. Proliferators-activated- receptor-y coactivator-1α (PGC-1α) is indispensable in controlling the gene expression which takes part in oxidative phosphorylation as well as the production of adenosine tri-phosphate (ATP). The muscle-specific expression of PGC-1α improves physical activities. It is proved by the results of PGC-1α transgenic mice in VO2max stress/loading tests that showed increased oxidative capacity.
The discovery of hypoxia-inducible factors (HIF) supported our understanding of the complex mechanism responding to hypoxic stress. It occurs in physical activities done with high-intensity. HIF are key regulators of almost 200 genes which participate in energy metabolism, glucose transport, angiogenesis and eritropoesis. They are ineffective in case of HIF-1 and HIF-2 normoxia, but they are active in hypoxic circumstances. The occurrence of HIF varies: while HIF-1 is expressed in most of the fibres, the expression of HIF-2 characterizes only few fibre types, for example, endothelium. HIF-1 as the primary transcription response factor to hypoxic stress often stimulates glycolysis and angiogenesis in case of low oxygen supply. Basically the genes controlled by HIF, such as proteins stimulating the production of RBC (red blood cells) and glycolytic enzyme encoders are crucial to achieve high level of anaerobic production, while pO2 is low. Removing HIF-1α brings about adaptive changes in skeletal muscle which is similar to the endurance physical activity. It proves the role of mitochondrial biogenesis suppression of HIF-1α in normal fibres. Similar changes occur in the polymorphism (Pro582Ser) of HIF-1α gene. The gene polymorphism of HIF-1α can be used as a genetic marker in strength/power-driven athletes. The HIF-2α encoded by endothelial domain protein-1 (EPAS-1) as sensor co-ordinates the adaptation of cardiovascular function, muscle activity and energy demand. The DNS variants of EPAS-1 affect the aerobic and anaerobic metabolism while maintaining maximum performance. For example, HIF-2α is responsible for Tibetans’ adaptation to high-altitude air.
While examining the variants of predestined genes within sports demanding strength and stamina haemoglobin should also be dealt with. The haemoglobin-beta (HBB) is responsible for oxygen supply. The crucial role of haemoglobin is well known. Its elevated level in blood increases VO2max and endurance capacity. In the intron 2 of haemoglobin gene in homozygote (+16C/C or – 551C/C) forms oxygen demand decreases in case of running. This explains the adaptability of individual variance to circulatory systems.
The polymorphism of the gene (EPOR) which encodes erythropoietin receptor participating in blood production, the nitric-oxide synthase-3 (NOS3) and gene variants of bradykinin receptor B2 (BDKRB2) are also in connection with the increase of oxygen supply of muscles, thus also improving endurance and stamina. The genomic examination of glucose- and insulin metabolism phenotypes during trainings demanding lots of energy involves three QTL. One of them on 19q13 is the identified skeletal muscle glycogen synthase (GYSI) gene locus focusing on the effectiveness of glucose utilization (an uncontrolled insulin effect, which mediates the intake from sugar plasma) affects the response to trainings.
The genes of adrenergic receptors are crucial regarding performance and achievement. The gene expression of beta2-adrenergic receptor (ADRB2) affects the endurance phenotype by regulating the lipid mobilization and using energy from fat. The polymorphism of Arg16Gly gene can be related to the Europeans’ endurance condition.
The cardio-respiratory condition can be characterized by the duration of heart rate after physical activities. This process depends on the muscarinic type cholinergic receptor-2 (CHMR2) gene variant. CHMR2 has a key role in the chronotropic response of the heart. Thus the DNS sequence change of CHMR2 locus may modify the sedation of the heart regarding lifestyle which lacks physical activity as well as after a shorter training trying to develop endurance.
By endothelial cell proliferation and migration the vascular endothelial growth factor affects the peripheral circulation. Those individuals who have at least one copy of AAG or CGC promoter region haplotype their VO2max will be higher after aerobic trainings than those who have only AGG and/or CGG haplotype.
Figure 1. Gene expression relating to endurance.
The production of reactive oxygen radicals is negatively regulated by mitochondrial uncoupling protein-2 (UCP2). Although the relationship between UPC2 gene and the resting metabolic rate has already been detected, but how it relates to physical activity is still unknown.