ACTN3 genotype, athletic status, and life course physical capability: meta-analysis of the published literature and findings from nine studies

Abstract

The ACTN3 R577X (rs1815739) genotype has been associated with athletic status and muscle phenotypes, although not consistently. Our objective was to conduct a meta-analysis of the published literature on athletic status and investigate its associations with physical capability in several new population-based studies. Relevant data were extracted from studies in the literature, comparing genotype frequencies between controls and sprint/power and endurance athletes. For life course physical capability, data were used from two studies of adolescents and seven studies in the Healthy Ageing across the Life Course (HALCyon) collaborative research program, involving individuals aged between 53 and 90+ years. We found evidence from the published literature to support the hypothesis that in Europeans the RR genotype is more common among sprint/power athletes compared with their controls. There is currently no evidence that the X allele is advantageous to endurance athleticism. We found no association between R577X and grip strength (P = 0.09, n = 7,672 in males; P = 0.90, n = 7,839 in females), standing balance, timed get up and go, or chair rises in our studies of physical capability. The ACTN3 R577X genotype is associated with sprint/power athletic status in Europeans, but does not appear to be associated with objective measures of physical capability in the general population.

Figure 1

Associations between ACTN3 R577X genotype (RR vs. RX + XX) and sprint/power athletic status from the literature. Arrow indicates the confidence interval extends beyond the plot axis. Stratified by ancestral group. Effects are given as odds ratios (OR) and 95% confidence intervals (CI). Points and the horizontal lines represent the study effect sizes and their 95% CIs. Sizes of the squares represent the weights of the studies. Diamonds represent the summary effects and their 95% CIs. I–V: inverse-variance, fixed effect model. D + L: DerSimonian & Laird, random effects model.

Figure 2

Associations between ACTN3 R577X genotype (XX vs. RX + RR) and endurance athletic status from the literature. Arrow indicates the confidence interval extends beyond the plot axis. Stratified by ancestral group. Effects are given as odds ratios (OR) and 95% confidence intervals (CI). Points and the horizontal lines represent the study effect sizes and their 95% CIs. Sizes of the squares represent the weights of the studies. Diamonds represent the summary effects and their 95% CIs. I–V: inverse-variance, fixed effect model. D + L: DerSimonian & Laird, random effects model.

Figure 3

Associations between ACTN3 R577X genotype and grip strength. Studies ordered by overall median age. Effects are given as per X allele change in grip strength (z-score) and 95% confidence intervals (CI). Points and the horizontal lines represent the study effect sizes and their 95% CIs. Sizes of the squares represent the weights of the studies. Diamonds represent the summary effects and their 95% CIs. I–V: inverse-variance, fixed effect model. D + L: DerSimonian & Laird, random effects model.

Figure 4

Associations between ACTN3 R577X genotype and timed get up and go/walk. Studies ordered by overall median age. Effects are given as per X allele change in timed get up and go or walk (z-score) and 95% confidence intervals (CI). Points and the horizontal lines represent the study effect sizes and their 95% CIs. Sizes of the squares represent the weights of the studies. Diamonds represent the summary effects and their 95% CIs. I–V: inverse-variance, fixed effect model. D + L: DerSimonian & Laird, random effects model.

Figure 5

Associations between ACNT3 R577X genotype and timed chair rises. Studies ordered by overall median age. Effects are given as per X allele change in timed chair rises (z-score) and 95% confidence intervals (CI). Points and the horizontal lines represent the study effect sizes and their 95% CIs. Sizes of the squares represent the weights of the studies. Diamonds represent the summary effects and their 95% CIs. I–V: inverse-variance, fixed effect model. D + L: DerSimonian & Laird, random effects model.

Figure 6

Associations between ACTN3 R577X genotype and poor standing balance. Poor standing balance defined as inability to complete 30 sec, or 5 sec of the full tandem in ELSA. Studies ordered by overall median age. Effects are given as poor balance odds ratio (OR) per X allele and 95% confidence intervals (CI). Points and the horizontal lines represent the study effect sizes and their 95% CIs. Sizes of the squares represent the weights of the studies. Diamonds represent the summary effects and their 95% CIs. I–V: inverse-variance, fixed effect model. D + L: DerSimonian & Laird, random effects model.