Department of Geriatrics, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi, China.
Department of Geriatrics and Special Needs Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China.
Front Endocrinol (Lausanne). 2024 Oct 23;15:1422472. doi: 10.3389/fendo.2024.1422472. eCollection 2024.
Insulin-like growth factor (IGF) is closely associated with sarcopenia, yet the causal relationship of this association remains unclear. This study aims to explore the potential causal relationship between members of the IGF family and sarcopenia from a genetic perspective through bidirectional Mendelian randomization (MR) analysis using two-sample datasets.
Five genetically predicted factors of the IGF family (IGF-1, IGF-1R, IGF-2R, IGFBP-3, IGFBP-7) as one sample, while four relevant features of sarcopenia (low hand grip strength, appendicular lean mass, whole body fat-free mass, and walking pace) as another sample, in conducting a two-sample MR analysis.
The forward MR results of the relationship between IGF and sarcopenia showed that elevated levels of IGF-1 reduced the risk of low hand grip strength (OR = 0.936, 95% CI=0.892-0.983, P = 0.008) and increased appendicular lean mass of the extremities and whole body fat-free mass (OR = 1.125, 95% CI=1.070-1.182,P = 0.000; OR =1.076, 95% CI=1.047-1.106, P=0.000), reduced the risk of sarcopenia. Elevated IGF-1R also favored an increase in whole body fat-free mass (OR=1.023, 95% CI=1.008-1.038, P =0.002), and the appendicular lean mass trait was more pronounced with elevated IGFBP-3 and IGFBP-7 (OR=1.034, 95% CI=1.024-1.044, P =0.000; OR=1.020, 95% CI=1.010-1.030, P=0.000). Inverse MR results of the effect of sarcopenia on IGF showed that decreased hand grip strength may elevate IGF-1 levels (OR=1.243, 95% CI=1.026-1.505,P =0.027), whereas improvements in appendicular lean mass, whole body fat-free mass traits, and increased walking pace decreased IGF-1 levels (OR=0.902, 95% CI: 0.877-0.927, P = 0.000; OR=0.903, 95% CI=0.859-0.949,P = 0.000; OR=0.209, 95% CI=0.051-0.862,P = 0.045). Also decreased hand grip strength may elevate IGF-1R levels (OR=1.454, 95% CI=1.108-1.909, P =0.007), and appendicular lean mass stimulated high expression of IGFBP-1 (OR=1.314, 95% CI=1.003-1.722, P =0.047). Heterogeneity and pleiotropy were not detected in all results, and the results were stable and reliable.
There is a bi-directional causal association between IGF family members and the risk of sarcopenia, which provides a more adequate basis for early biological monitoring of sarcopenia and may provide new targets for early intervention and treatment of sarcopenia.
胰岛素样生长因子（IGF）与肌肉减少症密切相关，但这种关联的因果关系尚不清楚。本研究旨在通过使用两样本数据集的双向孟德尔随机化（MR）分析，从遗传角度探讨 IGF 家族成员与肌肉减少症之间的潜在因果关系。
将 IGF 家族的五个遗传预测因子（IGF-1、IGF-1R、IGF-2R、IGFBP-3、IGFBP-7）作为一个样本，而将四个与肌肉减少症相关的特征（低手握力、四肢瘦体重、全身去脂体重和步行速度）作为另一个样本，进行两样本 MR 分析。
IGF 与肌肉减少症之间关系的正向 MR 结果表明，IGF-1 水平升高降低了低手握力的风险（OR=0.936，95%CI=0.892-0.983，P=0.008），增加了四肢瘦体重和全身去脂体重（OR=1.125，95%CI=1.070-1.182，P=0.000；OR=1.076，95%CI=1.047-1.106，P=0.000），降低了肌肉减少症的风险。IGF-1R 水平升高也有利于全身去脂体重的增加（OR=1.023，95%CI=1.008-1.038，P=0.002），而 IGFBP-3 和 IGFBP-7 水平升高时四肢瘦体重特征更为明显（OR=1.034，95%CI=1.024-1.044，P=0.000；OR=1.020，95%CI=1.010-1.030，P=0.000）。肌肉减少症对 IGF 影响的反向 MR 结果表明，握力下降可能会升高 IGF-1 水平（OR=1.243，95%CI=1.026-1.505，P=0.027），而四肢瘦体重、全身去脂体重特征的改善以及步行速度的提高会降低 IGF-1 水平（OR=0.902，95%CI：0.877-0.927，P=0.000；OR=0.903，95%CI=0.859-0.949，P=0.000；OR=0.209，95%CI=0.051-0.862，P=0.045）。握力下降也可能会升高 IGF-1R 水平（OR=1.454，95%CI=1.108-1.909，P=0.007），而四肢瘦体重会刺激 IGFBP-1 的高表达（OR=1.314，95%CI=1.003-1.722，P=0.047）。所有结果均未检测到异质性和偏倚，且结果稳定可靠。
IGF 家族成员与肌肉减少症的风险之间存在双向因果关系，这为肌肉减少症的早期生物学监测提供了更充分的依据，可能为肌肉减少症的早期干预和治疗提供新的靶点。
