School of Kinesiology, Auburn University, Auburn, AL, USA.
Duke Molecular Physiology Institute, Duke University School of Medicine, Duke University, Durham, NC, USA.
FASEB J. 2021 May;35(5):e21587. doi: 10.1096/fj.202100113RR.
We examined the association between genotype and resistance training-induced changes (12 wk) in dual x-ray energy absorptiometry (DXA)-derived lean soft tissue mass (LSTM) as well as muscle fiber cross-sectional area (fCSA; vastus lateralis; n = 109; age = 22 ± 2 y, BMI = 24.7 ± 3.1 kg/m ). Over 315 000 genetic polymorphisms were interrogated from muscle using DNA microarrays. First, a targeted investigation was performed where single nucleotide polymorphisms (SNP) identified from a systematic literature review were related to changes in LSTM and fCSA. Next, genome-wide association (GWA) studies were performed to reveal associations between novel SNP targets with pre- to post-training change scores in mean fCSA and LSTM. Our targeted investigation revealed no genotype-by-time interactions for 12 common polymorphisms regarding the change in mean fCSA or change in LSTM. Our first GWA study indicated no SNP were associated with the change in LSTM. However, the second GWA study indicated two SNP exceeded the significance level with the change in mean fCSA (P = 6.9 × 10 for rs4675569, 1.7 × 10 for rs10263647). While the former target is not annotated (chr2:205936846 (GRCh38.p12)), the latter target (chr7:41971865 (GRCh38.p12)) is an intron variant of the GLI Family Zinc Finger 3 (GLI3) gene. Follow-up analyses indicated fCSA increases were greater in the T/C and C/C GLI3 genotypes than the T/T GLI3 genotype (P < .05). Data from the Auburn cohort also revealed participants with the T/C and C/C genotypes exhibited increases in satellite cell number with training (P < .05), whereas T/T participants did not. Additionally, those with the T/C and C/C genotypes achieved myonuclear addition in response to training (P < .05), whereas the T/T participants did not. In summary, this is the first GWA study to examine how polymorphisms associate with the change in hypertrophy measures following resistance training. Future studies are needed to determine if the GLI3 variant differentiates hypertrophic responses to resistance training given the potential link between this gene and satellite cell physiology.
我们研究了基因型与阻力训练诱导的变化（12 周）之间的关联，这些变化是通过双能 X 射线吸收法（DXA）得出的瘦软组织质量（LSTM）以及肌肉纤维横截面积（fCSA；股外侧肌；n=109；年龄=22±2 岁，BMI=24.7±3.1kg/m2）。使用 DNA 微阵列对肌肉进行了超过 315000 个遗传多态性的检测。首先，进行了一项有针对性的调查，其中从系统文献综述中确定的单核苷酸多态性（SNP）与 LSTM 和 fCSA 的变化有关。接下来，进行了全基因组关联（GWA）研究，以揭示与训练前后平均 fCSA 和 LSTM 变化分数相关的新 SNP 靶点之间的关联。我们的针对性研究表明，对于平均 fCSA 的变化或 LSTM 的变化，12 种常见多态性的基因型与时间没有相互作用。我们的第一项 GWA 研究表明，没有 SNP 与 LSTM 的变化有关。然而，第二项 GWA 研究表明，两个 SNP 与平均 fCSA 的变化相关（rs4675569 的 P=6.9×10，rs10263647 的 P=1.7×10）。虽然前者的靶标没有注释（chr2：205936846（GRCh38.p12）），但后者的靶标（chr7：41971865（GRCh38.p12））是 Gli 家族锌指 3（GLI3）基因的内含子变异。后续分析表明，与 T/T GLI3 基因型相比，GLI3 基因型为 T/C 和 C/C 的 fCSA 增加更大（P<.05）。奥本队列的数据还显示，训练后 T/C 和 C/C 基因型的参与者卫星细胞数量增加（P<.05），而 T/T 参与者则没有。此外，T/C 和 C/C 基因型的参与者对训练有肌核添加反应（P<.05），而 T/T 参与者则没有。总之，这是第一项研究多态性如何与阻力训练后肥大测量变化相关的 GWA 研究。需要进一步的研究来确定 GLI3 变体是否可以区分对阻力训练的肥大反应，因为该基因与卫星细胞生理学之间存在潜在联系。
