Role of ACTN3 (R577X) in metabolic and contractile properties of human muscle.

Three studies will investigate the role of the stop codon polymorphism in the ACTN3 gene. ACTN3 codes for the alpha-actinin-3 protein, with its unique location in the Z-line of fast contractile muscle fibers. ACTN2 is present in Z-lines of all fiber types. Alpha-actinins are important structural components of the Z-line, but also interact with many other proteins, indicating a regulatory function in contractility and metabolic characteristics of the muscle fiber. In about 20% of all Caucasians, the alpha-actinin protein is completely lacking as they are homozygote carriers of a stop codon mutation (577X), however, no clear muscle pathology is related to this status. There is still lack of evidence about metabolic and contractile properties that are associated with XX or RR genotype status. A first study aims to investigate the (increased) oxidative capacity of fast muscle fibers in XX-carriers. This was an observation in the Actn3-/- knock out mouse. In a second study, improved recuperation in XX-carriers is studied after a fatiguing protocol, both as an acute effect and after training. In a third study, contractile properties of XX and RR fibers are studied in a single fiber study protocol.

Keywords:Talent detection, Oxidative capacity, Functional genomics, Alpha-actinins, Contractility

Disciplines:Biochemistry and metabolism, Medical biochemistry and metabolism, Genetics, Systems biology, Molecular and cell biology