Huygens W, Thomis M A I, Peeters M W, Aerssens J, Vlietinck R, Beunen G P
Research Center for Exercise and Health, Faculty of Kinesiology and Rehabilitation Sciences, Katholieke Universiteit Leuven, Belgium.
Physiol Genomics. 2005 Aug 11;22(3):390-7. doi: 10.1152/physiolgenomics.00010.2005. Epub 2005 May 24.
This study reports the results of a multipoint linkage study that aims to unravel the genetic basis of muscle strength and muscle mass in humans. Myostatin (GDF8) is known to be a strong inhibitor of muscle growth in animals. However, studies examining human myostatin polymorphisms are rare and are limited to the GDF8 gene itself. Here, the contribution to isometric and concentric knee strength of nine key proteins involved in the myostatin pathway is studied in a nonparametric multipoint linkage analysis by means of a variance components and regression method. A sample of 367 healthy young male siblings was phenotyped on an isokinetic dynamometer and genotyped for markers of the myostatin pathway genes. Three of the loci were found significantly linked with a quantitative trait locus (QTL) for knee muscle strength. First, D13S1303 showed replication of an explorative single-point linkage study with a maximum LOD score of 2.7 (P = 0.0002). Second, maximum LOD scores of 3.4 (P = 0.00004) and 3.3 (P = 0.00005) were observed for markers D12S1042 and D12S85, respectively, at 12q12-14. Finally, marker D12S78 showed an LOD score of 2.7 at 12q22-23. We conclude that several genes involved in the myostatin pathway, but not the myostatin gene itself, are important QTLs for human muscle strength. An additional set of valuable candidate genes that were not part of the myostatin pathway was found in the chromosome 12 and 13 genomic regions.
本研究报告了一项多点连锁研究的结果，该研究旨在揭示人类肌肉力量和肌肉质量的遗传基础。已知肌肉生长抑制素（GDF8）是动物肌肉生长的强效抑制剂。然而，研究人类肌肉生长抑制素多态性的研究很少，且仅限于GDF8基因本身。在此，通过方差成分和回归方法，在非参数多点连锁分析中研究了肌肉生长抑制素途径中9种关键蛋白对等长和向心膝关节力量的贡献。对367名健康年轻男性同胞的样本在等速测力计上进行表型分析，并对肌肉生长抑制素途径基因的标记进行基因分型。发现其中3个位点与膝关节肌肉力量的数量性状位点（QTL）显著连锁。首先，D13S1303显示了一项探索性单点连锁研究的重复结果，最大LOD值为2.7（P = 0.0002）。其次，在12q12 - 14处，标记D12S1042和D12S85的最大LOD值分别为3.4（P = 0.00004）和3.3（P = 0.00005）。最后，标记D12S78在12q22 - 23处的LOD值为2.7。我们得出结论，肌肉生长抑制素途径中的几个基因，而非肌肉生长抑制素基因本身，是人类肌肉力量的重要QTL。在12号和13号染色体基因组区域中发现了一组不属于肌肉生长抑制素途径的有价值的候选基因。
