Linkage of myostatin pathway genes with knee strength in humans

Abstract

This study was the first to explore the potential role of the myostatin (GDF8) pathway in relation to muscle strength and estimated muscle cross-sectional area in humans using linkage analysis with a candidate gene approach. In young male sibs (n = 329) 11 polymorphic markers in or near 10 candidate genes from the myostatin pathway were genotyped. Muscle mass was estimated by anthropometric measurements, and maximal knee strength was evaluated using isokinetic dynamometers (Cybex NORM). Single-point nonparametric variance components and linear quantitative trait locus regression linkage analysis methods were used. Linkage patterns were observed between knee extension and flexion peak torque with markers D2S118 (GDF8), D6S1051 (CDKN1A), and D11S4138 (MYOD1), and a maximum LOD score of 2.63 (P = 0.0002) was observed with D2S118. The ratios of peak torque over muscle and bone area of the midthigh of the lower contraction velocity (60 degrees/s) showed more frequently significant LOD scores than the torques at high velocity (240 degrees/s). Although myostatin is physiologically more related to muscle mass through possible effects of hyperplasia and hypertrophy than it is to strength, only two estimated muscle cross-sectional areas were marginally linked (LOD 1.06 and 1.07, P = 0.01) with marker D2S118 near GDF8 (2q32.2). The present results gave suggestive evidence that the myostatin pathway might be important for strength phenotypes, and GDF8, CDKN1A, and MYOD1 are potential candidate regions for a further and denser mapping with respect to these phenotypes.

Genes and the ageing muscle: a review on genetic association studies

“…Myostatin gene The myostatin (MSTN; or growth differentiation factor 8) gene (Huygens et al 2004) is receiving growing attention in the last years. The MSTN gene encodes myostatin, a skeletal musclespecific secreted peptide that functions mainly to modulate myoblast proliferation and thus muscle mass and strength .…”

“…Despite controversy existing with regards to adults (Kostek et al 2009), the MSTN K153R polymorphism is likely associated with muscle phenotypes in old people, with the infrequent mutant R allele possibly exerting a negative influence (Ferrell et al 1999;Huygens et al 2004;Seibert et al 2001). In a cohort of old African-American women, Seibert et al reported lower muscle strength in those who carried the variant 153R allele (Seibert et al 2001).…”

Association of the K153R polymorphism in the myostatin gene and extreme longevity

“…Accelerated age loss of muscle strength is associated with higher mortality risk (Metter et al 2004;Ruiz et al 2008); as such, genes potentially associated with higher preservation of muscle function at late life could be associated not only with healthy ageing and lower disability risk but also with longevity. One such candidate is the myostatin (MSTN or growth differentiation factor 8) gene (Huygens et al 2004).…”

The K153R variant in the myostatin gene and sarcopenia at the end of the human lifespan

“…The myostatin (MSTN or growth differentiation factor 8, GDF8 [MIM601788]) gene is receiving growing attention (Huygens et al 2004). It encodes myostatin, a skeletal muscle-specific secreted peptide that functions to limit muscle growth (McPherron et al 1997).…”

“…Such low allelic frequency certainly limits the possibility of studying large groups of people carrying the R variant. Though controversy exists with regards to adults (Kostek et al 2009), the K153R polymorphism is associated with muscle strength, with the infrequent mutant R allele possibly exerting a negative influence in old (yet <80 years) Caucasian people (Ferrell et al 1999;Huygens et al 2004;Seibert et al 2001).…”