SynthesisJournal of physiological anthropology2026
Association between the ACTN3 R577X polymorphism and skeletal muscle mass: a systematic review and meta-analysis.
Synthesis in Journal of physiological anthropology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundThe ACTN3 R577X polymorphism is one of the genetic factors influencing skeletal muscle mass. Although several studies have reported that the X allele of the ACTN3 R577X polymorphism is associated with reduced muscle mass, others have found no significant relationship between genotype and muscle mass. These inconsistencies may be explained by differences in background characteristics of the study populations, such as sex, age, ethnicity, and measurement site. This systematic review and meta-analysis aimed to clarify the association between the ACTN3 R577X polymorphism and skeletal muscle mass. In addition, we investigated whether the effect of the ACTN3 gene is modified by population background. MAIN BODY: A total of 34 cohorts (9,496 participants) derived from 24 studies were included in the meta-analysis. In the overall analysis under the dominant model for the X allele (RR vs. RX + XX), the ACTN3 genotype showed a significant effect on skeletal muscle mass (SMD [95% CI] = - 0.08 [- 0.15 to - 0.02], p = 0.014), with the RX + XX group exhibiting lower skeletal muscle mass compared with the RR group. In contrast, the recessive model (RR + RX vs. XX) did not yield a statistically significant effect (SMD [95% CI] = - 0.02 [- 0.12 to 0.07], p = 0.616). Under the additive model, a trend toward an effect was observed (per-allele; β [95% CI] = - 0.05 [- 0.10 to 0.01], p = 0.078). Moderate heterogeneity was observed across all models (dominant: I
conclusionThe ACTN3 R577X polymorphism showed a small association with skeletal muscle mass under the X-allele dominant model, suggesting that this association may be detectable even in heterozygous individuals. Although measurement site may modulate this association, none of the examined factors substantially explained the observed heterogeneity when considered individually. The remaining variability may reflect combinations of background characteristics that were not fully captured by single-factor analyses. Further studies accounting for background characteristics are warranted to clarify the genetic contribution of ACTN3 R577X to skeletal muscle mass.
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