Association of Variation in ACTN3, MYOZ2 and MYOZ3 with Complex Quantitative Performance Phenotypes in Lithuanian Athletes and Controls

Abstract

Recent findings have shown that ACTN3 genotype regulates calcineurin signalling and thus muscle performance in mice. The aim of the present study was first to investigate associations of ACTN3 genotype with quantitative performance-related phenotypes in a cohort of native Lithuanian athletes and controls. The second aim was to identify variants within the Calsarcin family that were of a high enough frequency within the European population and investigate variation within these genotypes on performance-related associations. 407 participants (210 athletes, 197 controls: age 22 ± 4 years, BMI 23 ± 2 kg/m2) performed a range of tests including: anthropometric tests; isokinetic dynamometry; 30 m sprint, counter-movement jump; standing jump; 30 second Wingate test; and a V̇o2MAX test across three separate testing sessions. DNA from venous blood samples was genotyped through standard PCR and RFLP processes. ACTN3 R577X SNP R-allele carriers were faster than XX-homozygotes in a 0-10m stage of a 30m sprint (p < 0.01). Variation was identified at a suitable level for Calsarcin-1 (MYOZ2) and Calsarcin-3 (MYOZ3). As Calsarcins tether calcineurin at the sarcomeric z-line, it was hypothesised that any variation within the Calsarcin genes may alter calcineurin signalling and thus athletic performance. MYOZ2 SNP rs9995277 (Calsarcin-1) G-allele was not associated with any performance phenotype. MYOZ3 SNP rs116090320 (Calsarcin-3) G-allele carriers showed significantly increased relative V̇O2MAX (p = 0.01) and significantly lower isokinetic upper arm flexion strength at 90 d/sec (N•m, p < 0.01) compared to AA-homozygotes. In conclusion, we are the first group to identify functional variation within genes encoding members of the Calsarcin family and have demonstrated for the first time that variation within MYOZ3 affects performance-related phenotypes in humans.