Chagnon Y C, Borecki I B, Pérusse L, Roy S, Lacaille M, Chagnon M, Ho-Kim M A, Rice T, Province M A, Rao D C, Bouchard C
Department of Social and Preventive Medicine, Faculty of Medicine, Laval University, Ste-Foy, Quebec, Canada.
Metabolism. 2000 Feb;49(2):203-7. doi: 10.1016/s0026-0495(00)91299-x.
Fat-free mass (FFM) consists mostly of skeletal muscle and bone tissues, and identification of the genes and molecular mechanisms involved in the control of FFM would have implications for the understanding of sarcopenia and potentially osteoporesis associated with aging, as well as the response to starvation, refeeding, anorexia, and any other conditions in which lean body mass is important. A genome-wide search for genes related to body leanness has been completed in the Quebec Family Study (QFS). Microsatellite markers (N = 292) from the 22 autosomal chromosomes were typed. The mean spacing of the markers was 11.9 centimorgans (cM) (range, <0.1 to 41). FFM was calculated from percent body fat, derived from underwater weighing, and body weight and was adjusted by regression for age and sex effects before analysis. A maximum of 336 sib pairs or 609 pairs of extended relatives were analyzed using single-point Haseman-Elston regression (SIBPAL and RELPAL) and multipoint variance component (SEGPATH) linkage analyses. Significant linkages were observed on chromosomes 15q25-q26 for a CA repeat within the insulin-like growth factor 1 receptor (IGF1R) gene (Lod score = 3.56) and at 18q12 with D18S877 (Lod score = 3.53) and D18S535 (Lod score = 3.58), 2 markers located 10 cM apart. A moderately significant linkage was also observed on chromosome 7p15.3 with the marker D7S1808 (Lod score = 2.72). The most obvious candidate genes within the regions identified by these linkages include the IGF1R on 15q and neuropeptide Y (NPY) and growth hormone-releasing hormone (GHRH) receptor on 7p. On 18q, the melanocortin receptor 4 (MC4R) is not likely the candidate gene for the observed linkage. This study represents the first genome-wide search for genes that may be involved in the regulation of the lean component of body mass in humans.
去脂体重（FFM）主要由骨骼肌和骨组织组成，识别参与FFM调控的基因和分子机制，对于理解与衰老相关的肌肉减少症以及潜在的骨质疏松症，以及对饥饿、再喂养、厌食症和任何其他瘦体重起重要作用的情况的反应都具有重要意义。在魁北克家族研究（QFS）中已完成了全基因组范围内与身体瘦度相关基因的搜索。对来自22条常染色体的微卫星标记（N = 292）进行了分型。标记的平均间距为11.9厘摩（cM）（范围，<0.1至41）。FFM是根据水下称重得出的体脂百分比、体重计算得出的，并在分析前通过回归对年龄和性别效应进行了调整。使用单点哈斯曼 - 埃尔斯顿回归（SIBPAL和RELPAL）和多点方差成分（SEGPATH）连锁分析，对最多336对同胞对或609对扩展亲属进行了分析。在15q25 - q26染色体上，胰岛素样生长因子1受体（IGF1R）基因内的一个CA重复序列处观察到显著连锁（Lod得分 = 3.56），在18q12处与D18S877（Lod得分 = 3.53）和D18S535（Lod得分 = 3.58）观察到显著连锁，这两个标记相距10 cM。在7p15.3染色体上，与标记D7S1808也观察到中度显著连锁（Lod得分 = 2.72）。这些连锁区域内最明显的候选基因包括15q上的IGF1R以及7p上的神经肽Y（NPY）和生长激素释放激素（GHRH）受体。在18q上，黑皮质素受体4（MC4R）不太可能是观察到的连锁的候选基因。这项研究是首次在全基因组范围内搜索可能参与人类体重瘦成分调控的基因。
