Familial aggregation of VO2max

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Familial aggregation of VO2max
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Design of genetic studies -1
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Design of genetic studies -2
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Performance/fitness phenotypes

• Fast growing after completion of Human Genome
  Project
• gt170 genes associated with performance or
  health-related fitness in 2006
• Only 29 in 2001

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Genes may affect performance, fitness
Rankinen T, MSSE, 2006
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ACTN3 and muscle performance

• Alpha-actinin 3
• R577X (arginine ? stop codon at codon 577)
• X-allele frequency 25-50 in different
  populations
• In patients with several muscular disorders X/X
  genotype complete absence of ACTN3 protein
• Only by chance, ACTN deficiency not deleterious
  because its function can be compensated by ACTN2
• X/X reduce performance in sprint or power-related
  sports

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ACE and endurance performance

• Angiotension-converting enzyme
• Angiotensinogen ? angiotensin II, vacoconstrictor
• 287 nucleotide insertion/deletion polymorphism
• Genotype no effect in VO2max
• Greater muscle efficiency in I/I compated to D/D
• Efficiency Work performed per unit energy
  expenditure
• No association at baseline potential gene x
  environment interaction
• Trainability
• D allele ?muscle growth?

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ACE polymorphism in Olympic runners
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Myostatin and muscle mass

• Disabled myostatin gene increase muscle size
• Mutation rare in humans

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Myostatin mutations in animals
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Molecular scouting?

• Exercise is a very complicated physiological
  function
• May involve more than 1 gene
• gt 100 genes turn on/off after a single bout of
  exercise
• Need to look for combination of genes
• Current techniques available
• Gene chips, computer aided

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Gene therapy and gene doping

• Gene therapy successfully used in several
  clinical conditions
• Somatic cell gene therapy
• Germ cell gene therapy
• Gene doping possible and may already being used
• 2006, a German coach asked for Repoxygen, a
  virus-based gene therapy product designed to
  deliver human EPO gene to muscle cells
• Originally used to treat severe anemia,
  successful in treating mice
• Almost impossible to detect
• Tissue sampling, DNA sequence

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