Cardiovascular and Respiratory Interface Section, National Heart and Lung Institute, Imperial College London, South Kensington Campus, London, United Kingdom.
Cutrale Perioperative and Ageing Group, Department of Bioengineering, Imperial College London, London, United Kingdom.
PLoS One. 2024 Aug 2;19(8):e0307268. doi: 10.1371/journal.pone.0307268. eCollection 2024.
Understanding genetic contributors to sarcopenia (age-related loss of muscle strength and mass) is key to finding effective therapies. Variants of the bradykinin receptor 2 (BDKRB2) have been linked to athletic and muscle performance. The rs1799722-9 and rs5810761 T alleles have been shown to be overrepresented in endurance athletes, possibly due to increased transcriptional rates of the receptor. These variants have been rarely studied in older people or people with sarcopenia.
We performed a post hoc sub-study of the Leucine and ACE (LACE) inhibitor trial, which enrolled 145 participants aged ≥70 years with low grip strength and low gait speed. Participants' blood samples were genotyped for rs179972 using TaqMan and rs5810761 by amplification through Hotstar Taq. Genotypes were compared with outcomes of physical performance and body composition measures.
Data from 136 individuals were included in the analysis. For rs1799722 the genotype frequency (TT: 17, CC: 48, CT: 71) remained in Hardy-Weinberg Equilibrium (HWE p = 0.248). There was no difference between the genotypes for six-Minute Walk Distance (6MWD) or Short Physical Performance Battery (SPPB). Men with the TT genotype had a significantly greater 6MWD than other genotypes (TT 400m vs CT 310m vs CC 314m, p = 0.027), and greater leg muscle mass (TT 17.59kg vs CT 15.04kg vs CC 15.65kg, p = 0.007). For rs5810761, the genotype frequency (-9-9: 31, +9+9: 43, -9+9: 60) remained in HWE (p = 0.269). The +9+9 genotype was associated with a significant change in SPPB score at 12 months (-9-9 0 vs -9+9 0 vs +9+9-1, p<0.001), suggesting an improvement. In men, the -9-9 genotype was associated with lower arm fat (-9-9 2.39kg vs -9+9 2.72kg vs +9+9 2.76kg, p = 0.019).
In men, the rs1799722 TT genotype was associated with longer 6MWD and greater leg muscle mass, while the rs5810761 -9-9 genotype was associated with lower arm fat mass.
了解导致肌肉减少症（与年龄相关的肌肉力量和质量损失）的遗传因素是寻找有效治疗方法的关键。缓激肽受体 2（BDKRB2）的变异与运动和肌肉表现有关。已经表明，rs1799722-9 和 rs5810761 T 等位基因在耐力运动员中过度表达，可能是由于受体的转录率增加。这些变体在老年人或肌肉减少症患者中很少被研究。
我们对亮氨酸和 ACE（LACE）抑制剂试验进行了事后亚研究，该试验招募了 145 名年龄≥70 岁、握力低和步速低的参与者。参与者的血液样本使用 TaqMan 对 rs179972 进行基因分型，使用 Hotstar Taq 通过扩增对 rs5810761 进行基因分型。将基因型与身体表现和身体成分测量的结果进行比较。
对 136 名个体的数据进行了分析。对于 rs1799722，基因型频率（TT：17，CC：48，CT：71）仍处于哈迪-温伯格平衡（HWE p = 0.248）。三种基因型在 6 分钟步行距离（6MWD）或简短身体表现电池（SPPB）方面没有差异。TT 基因型的男性 6MWD 明显大于其他基因型（TT 400m 与 CT 310m 与 CC 314m，p = 0.027），并且腿部肌肉质量更大（TT 17.59kg 与 CT 15.04kg 与 CC 15.65kg，p = 0.007）。对于 rs5810761，基因型频率（-9-9：31，+9+9：43，-9+9：60）仍处于 HWE（p = 0.269）。+9+9 基因型与 SPPB 评分在 12 个月时的显著变化相关（-9-9 0 与 -9+9 0 与 +9+9-1，p<0.001），表明有所改善。在男性中，-9-9 基因型与手臂脂肪减少相关（-9-9 2.39kg 与 -9+9 2.72kg 与 +9+9 2.76kg，p = 0.019）。
在男性中，rs1799722 TT 基因型与 6MWD 较长和腿部肌肉质量较大相关，而 rs5810761-9-9 基因型与手臂脂肪质量较低相关。
