Ran Shu, Liu Yong-Jun, Zhang Lei, Pei Yufang, Yang Tie-Lin, Hai Rong, Han Ying-Ying, Lin Yong, Tian Qing, Deng Hong-Wen
Center of System Biomedical Sciences, University of Shanghai for Science and Technology, Shanghai, People's Republic of China.
Department of Biostatistics and Bioinformatics, Tulane University, New Orleans, Louisiana, United States of America.
PLoS One. 2014 Mar 13;9(3):e89776. doi: 10.1371/journal.pone.0089776. eCollection 2014.
Skeletal muscle is a major component of the human body. Age-related loss of muscle mass and function contributes to some public health problems such as sarcopenia and osteoporosis. Skeletal muscle, mainly composed of appendicular lean mass (ALM), is a heritable trait. Copy number variation (CNV) is a common type of human genome variant which may play an important role in the etiology of many human diseases. In this study, we performed genome-wide association analyses of CNV for ALM in 2,286 Caucasian subjects. We then replicated the major findings in 1,627 Chinese subjects. Two CNVs, CNV1191 and CNV2580, were detected to be associated with ALM (p = 2.26×10(-2) and 3.34×10(-3), respectively). In the Chinese replication sample, the two CNVs achieved p-values of 3.26×10(-2) and 0.107, respectively. CNV1191 covers a gene, GTPase of the immunity-associated protein family (GIMAP1), which is important for skeletal muscle cell survival/death in humans. CNV2580 is located in the Serine hydrolase-like protein (SERHL) gene, which plays an important role in normal peroxisome function and skeletal muscle growth in response to mechanical stimuli. In summary, our study suggested two novel CNVs and the related genes that may contribute to variation in ALM.
骨骼肌是人体的主要组成部分。与年龄相关的肌肉质量和功能丧失会导致一些公共卫生问题，如肌肉减少症和骨质疏松症。骨骼肌主要由附属瘦体重（ALM）组成，是一种可遗传的性状。拷贝数变异（CNV）是人类基因组变异的一种常见类型，可能在许多人类疾病的病因中起重要作用。在本研究中，我们对2286名白种人受试者的ALM进行了全基因组CNV关联分析。然后我们在1627名中国受试者中重复了主要发现。检测到两个CNV，即CNV1191和CNV2580与ALM相关（p值分别为2.26×10⁻²和3.34×10⁻³）。在中国重复样本中，这两个CNV的p值分别为3.26×10⁻²和0.107。CNV1191覆盖一个基因，免疫相关蛋白家族的GTP酶（GIMAP1），该基因对人类骨骼肌细胞的存活/死亡很重要。CNV2580位于丝氨酸水解酶样蛋白（SERHL）基因中，该基因在正常过氧化物酶体功能和骨骼肌对机械刺激的生长反应中起重要作用。总之，我们的研究提出了两个新的CNV及其相关基因，它们可能导致ALM的变异。
