Walsh Sean, Metter E Jeffrey, Ferrucci Luigi, Roth Stephen M
2134 HHP Bldg., Department of Kinesiology, College of Health and Human Performance, University of Maryland, College Park, MD 20742-2611, and Clinical Research Branch, National Institute on Aging, Harbor Hospital, Baltimore, USA.
J Appl Physiol (1985). 2007 Jun;102(6):2142-8. doi: 10.1152/japplphysiol.01322.2006. Epub 2007 Mar 8.
Genetic variation in myostatin, a negative regulator of skeletal muscle, in cattle has shown remarkable influence on skeletal muscle, resulting in a double-muscled phenotype in certain breeds; however, DNA sequence variation within this gene in humans has not been consistently associated with skeletal muscle mass or strength. Follistatin and activin-type II receptor B (ACVR2B) are two myostatin-related genes involved in the regulation and signaling of myostatin. We sought to identify associations between genetic variation and haplotype structure in both follistatin and ACVR2B with skeletal muscle-related phenotypes. Three hundred fifteen men and 278 women aged 19-90 yr from the Baltimore Longitudinal Study of Aging were genotyped to determine respective haplotype groupings (Hap Groups) based on HapMap data. Whole body soft tissue composition was measured by dual-energy X-ray absorptiometry. Quadriceps peak torque (strength) was measured using an isokinetic dynamometer. Women carriers of ACVR2B Hap Group 1 exhibited significantly less quadriceps muscle strength (shortening phase) than women homozygous for Hap Group 2 (109.2+/-1.9 vs. 118.6+/-4.1 N.m, 30 degrees/s, respectively, P=0.036). No significant association was observed in men. Male carriers of follistatin Hap Group 3 exhibited significantly less total leg fat-free mass than noncarriers (16.6+/-0.3 vs. 17.5+/-0.2 kg, respectively, P=0.012). No significant associations between these haplotype groups were observed in women. These results indicate that haplotype structure at the ACVR2B and follistatin loci may contribute to interindividual variation in skeletal muscle mass and strength, although these data indicate sex-specific relationships.
肌肉生长抑制素是骨骼肌的一种负调节因子，其基因变异在牛中已显示出对骨骼肌有显著影响，导致某些品种出现双肌表型；然而，该基因在人类中的DNA序列变异与骨骼肌质量或力量并未始终存在关联。卵泡抑素和激活素II型受体B（ACVR2B）是两个与肌肉生长抑制素调节和信号传导相关的基因。我们试图确定卵泡抑素和ACVR2B基因变异及单倍型结构与骨骼肌相关表型之间的关联。对来自巴尔的摩纵向衰老研究的19至90岁的315名男性和278名女性进行基因分型，以根据HapMap数据确定各自的单倍型分组（单倍型组）。通过双能X线吸收法测量全身软组织成分。使用等速测力计测量股四头肌峰值扭矩（力量）。ACVR2B单倍型组1的女性携带者股四头肌力量（缩短期）明显低于单倍型组2的纯合女性（分别为109.2±1.9与118.6±4.1牛米，30度/秒，P = 0.036）。在男性中未观察到显著关联。卵泡抑素单倍型组3的男性携带者的总腿部去脂体重明显低于非携带者（分别为16.6±0.3与17.5±0.2千克，P = 0.012）。在女性中未观察到这些单倍型组之间的显著关联。这些结果表明，ACVR2B和卵泡抑素基因座的单倍型结构可能导致骨骼肌质量和力量的个体间差异，尽管这些数据表明存在性别特异性关系。
