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Linkage of myostatin pathway genes with knee strength in humans

¹ Department Sport and Movement Sciences, Faculty of Physical Education and Physiotherapy, Katholieke Universiteit Leuven, Maastricht 6229 ER, The Netherlands
² Division of Genetics and Molecular Cell Biology, Universiteit Maastricht, Maastricht 6229 ER, The Netherlands
³ Center for Human Genetics, Faculty of Medicine, Katholieke Universiteit Leuven, Leuven 3000, Belgium

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°/s) showed more frequently significant LOD scores than the torques at high velocity (240°/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.

quantitative trait locus; hypertrophy; fat-free mass; human performance; candidate gene

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