Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia-Analyses from the LACE randomised controlled trial.
Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia-Analyses from the LACE randomised controlled trial.
复制标题
DOI：
10.1371/journal.pone.0294330
复制
发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
衰老与身体成分的变化有关，包括肌肉质量的整体减少和脂肪质量的成比例增加。肌肉减少症的特征是肌肉质量和力量的损失。身体成分和肌肉力量至少部分由基因决定，因此肌肉生物学中重要途径的多态性（例如，激活素/肌生长抑制素信号通路）被假设为有助于肌肉减少症的发展。在LACE试验中，我们对110名老年肌肉减少症患者的DNA进行了横断面分析，并将DXA测量的局部身体成分与PCR测定的激活素1B受体（ACVR 1B）中两种多态性（rs 10783486，次要等位基因频率（MAF）= 0.26和rs 2854464，MAF = 0.26）的基因型进行了比较。在这个队列中，肌肉质量和力量都没有表现出与基因型的任何显著相关性。rs 10783486的初步分析显示，AA/AG基因型的男性比GG男性高（174± 7 cm vs 170± 5 cm，p = 0.023），手臂脂肪量（中位数高15%，p = 0.008）和腿部脂肪量（中位数高14%，p = 0.042）更高。校正身高后，手臂脂肪量仍显着较高（中位数高出4% padj = 0.024）。在女性中未观察到相关性（调整或未调整）。对rs 2854464等位基因的类似分析显示了类似的模式，次要等位基因（GG/AG）的存在与更高的身高（GG/AG = 174±7 cm vs AA = 170 ± 5 cm，p = 0.017）和更大的手臂脂肪量（中位数高16%，p = 0.023）相关。同样，在身高校正后，手臂脂肪的差异仍然存在。在单独分析的女性中未观察到类似的相关性。这些数据表明，ACVR 1B基因座的多态性变异可能与老年男性的身体组成。激活素/肌肉生长抑制素通路可能提供一种新的潜在靶点，以防止老年人的脂肪积累。
Ageing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle strength are at least in part genetically determined, consequently polymorphisms in pathways important in muscle biology (e.g., the activin/myostatin signalling pathway) are hypothesised to contribute to the development of sarcopenia. We compared regional body composition measured by DXA with genotypes for two polymorphisms (rs10783486, minor allele frequency (MAF) = 0.26 and rs2854464, MAF = 0.26) in the activin 1B receptor (ACVR1B) determined by PCR in a cross-sectional analysis of DNA from 110 older individuals with sarcopenia from the LACE trial. Neither muscle mass nor strength showed any significant associations with either genotype in this cohort. Initial analysis of rs10783486 showed that males with the AA/AG genotype were taller than GG males (174±7cm vs 170±5cm, p = 0.023) and had higher arm fat mass, (median higher by 15%, p = 0.008), and leg fat mass (median higher by 14%, p = 0.042). After correcting for height, arm fat mass remained significantly higher (median higher by 4% padj = 0.024). No associations (adjusted or unadjusted) were seen in females. Similar analysis of the rs2854464 allele showed a similar pattern with the presence of the minor allele (GG/AG) being associated with greater height (GG/AG = 174±7 cm vs AA = 170 ±5cm, p = 0.017) and greater arm fat mass (median higher by 16%, p = 0.023). Again, the difference in arm fat remained after correction for height. No similar associations were seen in females analysed alone. These data suggest that polymorphic variation in the ACVR1B locus could be associated with body composition in older males. The activin/myostatin pathway might offer a novel potential target to prevent fat accumulation in older individuals.
登录
查看更多内容
肌肉生长抑制素在哺乳动物脂肪量调节中的作用
影响因子：
4.5
作者：
Deng B;Zhang F;Wen J;Ye S;Wang L;Yang Y;Gong P;Jiang S
通讯作者：
Jiang S
影响因子：
--
作者：
Friedrichs M;Wirsdöerfer F;Flohé SB;Schneider S;Wuelling M;Vortkamp A
通讯作者：
Vortkamp A
影响因子：
4.6
作者：
Faron, Anton;Sprinkart, Alois M.;Luetkens, Julian A.
通讯作者：
Luetkens, Julian A.
影响因子：
4.8
作者：
Artaza, JN;Bhasin, S;Gonzalez-Cadavid, NF
通讯作者：
Gonzalez-Cadavid, NF
影响因子：
6.2
作者：
Chantry, Andrew D.;Heath, Debby;Croucher, Peter
通讯作者：
Croucher, Peter