Research Article: Association of the ACTN3 R577X (rs1815739) polymorphism with elite power sports: A meta-analysis

Date Published: May 30, 2019

Publisher: Public Library of Science

Author(s): Phuntila Tharabenjasin, Noel Pabalan, Hamdi Jarjanazi, Mikko Juhani Lammi.


The special status accorded to elite athletes stems from their uncommon genetic potential to excel in world-class power sports (PS). Genetic polymorphisms have been reported to influence elite PS status. Reports of associations between the α-actinin-3 gene (ACTN3) R577X polymorphism and PS have been inconsistent. In light of new published studies, we perform a meta-analysis to further explore the roles of this polymorphism in PS performance among elite athletes.

Multi-database literature search yielded 44 studies from 38 articles. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used in estimating associations (significance threshold was set at Pa ≤ 0.05) using the allele-genotype model (R and X alleles, RX genotype). Outlier analysis was used to examine its impact on association and heterogeneity outcomes. Subgroup analysis was race (Western and Asian) and gender (male/female)-based. Interaction tests were applied to differential outcomes between the subgroups, P-values of which were Bonferroni corrected (Pinteraction BC). Tests for sensitivity and publication bias were performed.

Significant overall R allele effects (OR 1.21, 95% CI 1.07–1.37, Pa = 0.002) were confirmed in the Western subgroup (OR 1.11, 95% CI 1.01–1.22, Pa = 0.02) and with outlier treatment (ORs 1.12–1.20, 95% CIs 1.02–1.30, Pa < 10−5–0.01). This treatment resulted in acquired significance of the RX effect in Asian athletes (OR 1.91, 95% CI 1.25–2.92, Pa = 0.003). Gender analysis dichotomized the RX genotype and R allele effects as significantly higher in male (OR 1.14, 95% CI 1.02–1.28, Pa = 0.02) and female (OR 1.58, 95% CI 1.21–2.06, Pa = 0.0009) athletes, respectively, when compared with controls. Significant R female association was improved with a test of interaction (Pinteraction BC = 0.03). The overall, Asian and female outcomes were robust. The R allele results were more robust than the RX genotype outcomes. No evidence of publication bias was found. In this meta-analysis, we present clear associations between the R allele/RX genotype in the ACTN3 polymorphism and elite power athlete status. Significant effects of the R allele (overall analysis, Western and female subgroups) and RX genotype (Asians and males) were for the most part, results of outlier treatment. Interaction analysis improved the female outcome. These robust findings were free of publication bias.

Partial Text

Exceptional performance during national/international-level competitions defines elite athletes [1]. Among elite power sports (PS) athletes, performance varies across countries, races and gender. This variation stems from genetic and environmental factors. It has been reported that genes play a substantial role in muscle function, specifically those involving the PS phenotype [2,3]. Genetic variants (i.e. polymorphisms) are vital in understanding the potential influence of genes on PS [4] but published outcomes have been variable [5,6]. Nevertheless, lines of evidence have catapulted the ACTN3 (α-actinin-3) polymorphism into prominence regarding its association with PS performance [7,8].

This meta-analysis has two principal findings: (i) overall associations of the R allele and RX genotype with PS performance were validated with outlier and subgroup treatments and (ii) the R allele was associated with Westerns and females whereas the RX genotype was associated with Asians and males. Gender-wise, the R allele effects differed between males and females. The significant Asian and male/female outcomes were the results of outlier treatment. This treatment impacted on heterogeneity (reduced or eliminated) of the gender outcomes, but not the Asian outcomes. Thus, retention of heterogeneity in the PSO Asian pooled effects warrants caution in its interpretation.