Huygens W, Thomis M A, Peeters M W, Aerssens J, Janssen R, Vlietinck R F, Beunen G
Department Sport and Movement Sciences, Faculty of Physical Education and Physiotherapy, Katholieke Universiteit Leuven, Maastricht 6229 ER, The Netherlands.
Physiol Genomics. 2004 May 19;17(3):264-70. doi: 10.1152/physiolgenomics.00224.2003.
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.
本研究首次采用候选基因方法进行连锁分析，以探究肌生成抑制素（GDF8）通路在人类肌肉力量和估计肌肉横截面积方面的潜在作用。对329名年轻男性同胞的肌生成抑制素通路中10个候选基因内部或附近的11个多态性标记进行了基因分型。通过人体测量估计肌肉质量，并使用等速测力计（Cybex NORM）评估最大膝关节力量。采用单点非参数方差成分法和线性数量性状基因座回归连锁分析方法。在膝关节伸展和屈曲峰值扭矩与标记D2S118（GDF8）、D6S1051（CDKN1A）和D11S4138（MYOD1）之间观察到连锁模式，与D2S118观察到的最大LOD得分为2.63（P = 0.0002）。较低收缩速度（60度/秒）时大腿中部肌肉和骨骼面积的峰值扭矩比与较高速度（240度/秒）时的扭矩相比，更频繁地显示出显著的LOD得分。尽管肌生成抑制素在生理上通过增生和肥大的可能作用与肌肉质量的关系比与力量的关系更大，但只有两个估计的肌肉横截面积与GDF8（2q32.2）附近的标记D2S118存在微弱连锁（LOD分别为1.06和1.07，P = 0.01）。目前的结果提供了提示性证据，表明肌生成抑制素通路可能对力量表型很重要，并且GDF8、CDKN1A和MYOD1是针对这些表型进行进一步更密集定位的潜在候选区域。
