2019 Association of Bradykinin receptor 2 variants with physical performance and muscle mass: findings from the LACE sarcopenia trial

Abstract

Abstract Introduction The kinin-kallikrein system has been implicated in muscle performance: bradykinin promotes glucose uptake and blood flow in muscle through bradykinin receptor 2 (BDKRB2). BDKRB2 variants include rs1799722 and rs5810761, where the T and -9 alleles respectively have associated with increased transcriptional rates and were overrepresented in endurance athletes. However, these variants have rarely been studied among older people or those with sarcopenia. Methods The Leucine and ACE inhibitor (ACE) trial enrolled 145 participants aged ≥70 years with low grip strength and low gait speed. Participants’ blood samples had DNA extracted and were genotyped for rs179972 using TaqMan and rs5810761 by amplification through Hotstar Taq (and visualised through 4% agarose gel electrophoresis). The differences in genotypes for each variant against physical performance measures (e.g. six-minute walk distance [6MWD]) was calculated using t-tests or Mann-Whitney tests where appropriate. Genotypes were also tested for Hardy-Weinberg equilibrium (HWE) using Chi-squared test. Results Data from 136 individuals were included in the analysis. For rs1799722, the genotype frequency (TT: 17, CC: 48, CT: 71) remained in HWE (p=0.248). No difference between TT and CC/CT group was seen for 6MWD, grip strength or SPPB. Among men, the TT genotype had greater 6MWD compared to CC/CT (400m vs 312m, p=0.007), and also greater leg muscle mass (17.6kg vs 15.3kg, p =0.005), but no difference was noted in women. For rs5810761, the genotype frequency (-9-9: 31, +9+9: 43, -9+9: 60) also remained in HWE (p=0.269). No difference between -9-9 and +9+9/+9-9 was seen for 6MWD, grip strength or SPPB. In men, but not women, -9-9 genotype had reduced arm fat baseline (1.85kg vs 2.72kg; p=0.005). Conclusion Among men, the TT genotype was associated with longer 6MW distance and higher leg muscle mass. The -9-9 genotype was associated with lower regional fat mass in men.