Laboratory of Molecular and Statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, People's Republic of China.
Hum Genet. 2012 Jan;131(1):1-31. doi: 10.1007/s00439-011-1040-7. Epub 2011 Jun 26.
Sarcopenia, which is characterized by a progressive decrease of skeletal muscle mass and function with aging, is closely related to several common diseases (such as cardiovascular and airway diseases) and functional impairment/disability. Strong genetic determination has been reported for muscle mass and muscle strength, two most commonly recognized and studied risk phenotypes for sarcopenia, with heritability ranging from 30 to 85% for muscle strength and 45-90% for muscle mass. Sarcopenia has been the subject of increasing genetic research over the past decade. This review is designed to comprehensively summarize the most important and representative molecular genetic studies designed to identify genetic factors associated with sarcopenia. We have methodically reviewed whole-genome linkage studies in humans, quantitative trait loci mapping in animal models, candidate gene association studies, newly reported genome-wide association studies, DNA microarrays and microRNA studies of sarcopenia or related skeletal muscle phenotypes. The major results of each study are tabulated for easy comparison and reference. The findings of representative studies are discussed with respect to their influence on our present understanding of the genetics of sarcopenia. This is a comprehensive review of molecular genetic studies of gene identification for sarcopenia, and an overarching theme for this review is that the currently accumulating results are tentative and occasionally inconsistent and should be interpreted with caution pending further investigation. Consequently, this overview should enhance recognition of the need to validate/replicate the genetic variants underlying sarcopenia in large human cohorts and animal. We believe that further progress in understanding the genetic etiology of sarcopenia will provide valuable insights into important fundamental biological mechanisms underlying muscle physiology that will ultimately lead to improved ability to recognize individuals at risk for developing sarcopenia and our ability to treat this debilitating condition.
肌肉减少症的特征是随着年龄的增长，骨骼肌质量和功能逐渐下降，与多种常见疾病（如心血管疾病和气道疾病）和功能障碍/残疾密切相关。肌肉质量和肌肉力量是肌肉减少症最常被认可和研究的两种风险表型，其遗传力范围分别为肌肉力量的 30%至 85%和肌肉质量的 45%至 90%。过去十年，肌肉减少症一直是遗传研究的热点。本综述旨在全面总结最重要和最具代表性的分子遗传学研究，以确定与肌肉减少症相关的遗传因素。我们系统地回顾了人类全基因组连锁研究、动物模型的数量性状基因座定位、候选基因关联研究、新报道的全基因组关联研究、肌肉减少症或相关骨骼肌表型的 DNA 微阵列和 microRNA 研究。每个研究的主要结果都列成表格，以便于比较和参考。代表性研究的结果根据它们对我们目前对肌肉减少症遗传理解的影响进行了讨论。这是一篇关于肌肉减少症基因鉴定的分子遗传学研究的综述，综述的一个主要主题是，目前积累的结果是暂定的，偶尔不一致，在进一步研究之前应谨慎解释。因此，本综述应增强对在大型人类队列和动物中验证/复制肌肉减少症潜在遗传变异的必要性的认识。我们相信，对肌肉减少症遗传病因的进一步理解将为肌肉生理学的重要基础生物学机制提供有价值的见解，最终将提高识别易患肌肉减少症的个体的能力，并提高我们治疗这种使人衰弱的疾病的能力。
