Frequent sequence variation in the human myostatin (GDF8) gene as a markerfor analysis of muscle-related phenotypes

Myostatin is a recently identified member of the transforming growth factor -beta family of regulatory factors, also known as growth and differentiatio n factor 8 (GDF8). The nucleotide sequence of human myostatin was determine d in 40 individuals. The invariant promoter contains a consensus MyoD bindi ng site, and the coding sequence contains five missense substitutions in co nserved amino acid residues (A55T, K153R, E164K, P198A, and I225T). Two of these, A55T in exon 1 and K153R in exon 2, are polymorphic in the general p opulation with significantly different allele frequencies in Caucasians and African Americans (P < 0.001). Neither of the common polymorphisms had a s ignificant impact on muscle mass response to strength training in either Ca ucasians or African Americans, although skewed allele frequencies preclude detection of small effects; These allelic variants provide markers for exam ining association between the myostatin gene and interindividual variation in muscle mass and differences in loss of muscle mass with (C) 1999 Academi c Press.