An intron variant of the GLI family zinc finger 3 (GLI3) gene differentiates resistance training-induced muscle fiber hypertrophy in younger men.
An intron variant of the GLI family zinc finger 3 (GLI3) gene differentiates resistance training-induced muscle fiber hypertrophy in younger men.
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DOI：
10.1096/fj.202100113rr
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发表时间：
2021-05
期刊：
影响因子：
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通讯作者：
Roberts MD
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文献类型：
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作者：
Vann CG;Morton RW;Mobley CB;Vechetti IJ;Ferguson BK;Haun CT;Osburn SC;Sexton CL;Fox CD;Romero MA;Roberson PA;Oikawa SY;McGlory C;Young KC;McCarthy JJ;Phillips SM;Roberts MD
我们检查了基因型与阻力训练诱导的双能X线能量吸收法（DXA）得出的瘦软组织质量（LSTM）变化（12周）以及肌纤维横截面积（fCSA;股外侧肌; n = 109;年龄= 22 ± 2岁，BMI = 24.7 ± 3.1 kg/m2）之间的相关性。使用DNA微阵列从肌肉中询问了超过315 000个遗传多态性。首先，进行了一项有针对性的调查，其中从系统性文献综述中识别的单核苷酸多态性（SNP）与LSTM和fCSA的变化相关。接下来，进行了全基因组关联（GWA）研究，以揭示新型SNP靶标与平均fCSA和LSTM训练前后变化评分之间的关联。我们的针对性调查显示，关于平均fCSA的变化或LSTM的变化，12种常见多态性没有基因型与时间的相互作用。我们的第一项GWA研究表明，SNP与LSTM的变化无关。然而，第二项GWA研究表明，两个SNP超过了平均fCSA变化的显著性水平（rs 4675569 P = 6.9 × 10-7，rs 10263647 P = 1.7 × 10-6）。虽然前一个靶标没有注释（chr 2：205936846（GRCh38.p12）），但后一个靶标（chr 7：41971865（GRCh38.p12））是GLI家族锌指3（GLI 3）基因的内含子变体。随访分析表明，T/C和C/C GLI 3基因型的fCSA增加大于T/T GLI 3基因型（P < .05）。来自奥本队列的数据还显示，T/C和C/C基因型的参与者随着训练表现出卫星细胞数量的增加（P <0.05），而T/T参与者则没有。此外，那些T/C和C/C基因型的参与者在训练中获得了肌球蛋白的增加（P <0.05），而T/T参与者则没有。总之，这是第一个研究多态性与阻力训练后肥大指标变化相关的GWA研究。未来的研究需要确定GLI 3变异体是否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。
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/m2). 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 × 10–7 for rs4675569, 1.7 × 10–6 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.