Cross-sectional relations of whole-blood miRNA expression levels and hand grip strength in a community sample.
Cross-sectional relations of whole-blood miRNA expression levels and hand grip strength in a community sample.
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在社区样本中，全血miRNA表达水平和手握力的横截面关系。
DOI：
10.1111/acel.12622
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发表时间：
2017-08
期刊：
影响因子：
7.8
通讯作者：
Larson MG
中科院分区：
文献类型：
--
作者：
Murabito JM;Rong J;Lunetta KL;Huan T;Lin H;Zhao Q;Freedman JE;Tanriverdi K;Levy D;Larson MG
MicroRNAs （miRNAs）调节基因表达，新数据表明miRNAs在骨骼肌生物学中发挥作用。我们试图在基于社区的样本中检查mirna与握力的关系。弗雷明汉心脏研究的后代和第三代参与者（n = 5668, 54%的女性，平均年龄55岁，范围24岁至90岁）使用早晨禁食样本的全血进行握力测量和miRNA分析。对握力（kg）与连续miRNA ‘ Cq ’值和二元miRNA表达进行线性混合效应回归建模。我们进行了综合miRNA-mRNA共表达分析，并检查了与握力相关的顶级mirna的生物学途径的富集。女性握力低于男性，并且随着年龄的增长而下降，男性平均握力为44.7 (10.0)kg，女性为26.5 (6.3)kg。在299个与握力相关的mirna中，93个（31%）的FDR q值< 0.05,54个（18%）的FDR q值< 0.01,15个（5%）的FDR q值< 0.001。对于几乎所有的miRNA -握力关联，增加miRNA浓度与增加握力相关。miR‐20a‐5p （FDR q 1.8 × 10−6）具有最显著的相关性，前15个mirna中有几个与骨骼肌相关，包括miR‐126‐3p， miR‐30a‐5p和miR‐30d‐5p。最主要的相关生物学途径包括代谢、趋化因子信号传导和泛素介导的蛋白质水解。我们对基于社区的血液中与握力相关的mirna样本进行了全面评估，为我们进一步了解肌肉力量的生物学提供了一个框架。
MicroRNAs (miRNAs) regulate gene expression with emerging data suggesting miRNAs play a role in skeletal muscle biology. We sought to examine the association of miRNAs with grip strength in a community‐based sample. Framingham Heart Study Offspring and Generation 3 participants (n = 5668 54% women, mean age 55 years, range 24, 90 years) underwent grip strength measurement and miRNA profiling using whole blood from fasting morning samples. Linear mixed‐effects regression modeling of grip strength (kg) versus continuous miRNA ‘Cq’ values and versus binary miRNA expression was performed. We conducted an integrative miRNA–mRNA coexpression analysis and examined the enrichment of biologic pathways for the top miRNAs associated with grip strength. Grip strength was lower in women than in men and declined with age with a mean 44.7 (10.0) kg in men and 26.5 (6.3) kg in women. Among 299 miRNAs interrogated for association with grip strength, 93 (31%) had FDR q value < 0.05, 54 (18%) had an FDR q value < 0.01, and 15 (5%) had FDR q value < 0.001. For almost all miRNA–grip strength associations, increasing miRNA concentration is associated with increasing grip strength. miR‐20a‐5p (FDR q 1.8 × 10−6) had the most significant association and several among the top 15 miRNAs had links to skeletal muscle including miR‐126‐3p, miR‐30a‐5p, and miR‐30d‐5p. The top associated biologic pathways included metabolism, chemokine signaling, and ubiquitin‐mediated proteolysis. Our comprehensive assessment in a community‐based sample of miRNAs in blood associated with grip strength provides a framework to further our understanding of the biology of muscle strength.
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