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The ACTN3 R577X Polymorphism Is Associated with Cardiometabolic Fitness in Healthy Young Adults.

ABSTRACT: Homozygosity for a premature stop codon (X) in the ACTN3 "sprinter" gene is common in humans despite the fact that it reduces muscle size, strength and power. Because of the close relationship between skeletal muscle function and cardiometabolic health we examined the influence of ACTN3 R577X polymorphism over cardiovascular and metabolic characteristics of young adults (n = 98 males, n = 102 females; 23 ± 4.2 years) from our Assessing Inherent Markers for Metabolic syndrome in the Young (AIMMY) study. Both males and females with the RR vs XX genotype achieved higher mean VO2 peak scores (47.8 ± 1.5 vs 43.2 ±1.8 ml/O2/min, p = 0.002) and exhibited higher resting systolic (115 ± 2 vs 105 ± mmHg, p = 0.027) and diastolic (69 ± 3 vs 59 ± 3 mmHg, p = 0.005) blood pressure suggesting a role for ACTN3 in the maintenance of vascular tone. We subsequently identified the expression of alpha-actinin 3 protein in pulmonary artery smooth muscle, which may explain the genotype-specific differences in cardiovascular adaptation to acute exercise. In addition, we utilized targeted serum metabolomics to distinguish between RR and XX genotypes, suggesting an additional role for the ACTN3 R577X polymorphism in human metabolism. Taken together, these results identify significant cardiometabolic effects associated with possessing one or more functional copies of the ACTN3 gene.

SUBMITTER: Deschamps CL

PROVIDER: S-EPMC4480966 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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The ACTN3 R577X Polymorphism Is Associated with Cardiometabolic Fitness in Healthy Young Adults.

Deschamps Chelsea L CL Connors Kimberly E KE Klein Matthias S MS Johnsen Virginia L VL Shearer Jane J Vogel Hans J HJ Devaney Joseph M JM Gordish-Dressman Heather H Many Gina M GM Barfield Whitney W Hoffman Eric P EP Kraus William E WE Hittel Dustin S DS

PloS one 20150624 6

Homozygosity for a premature stop codon (X) in the ACTN3 "sprinter" gene is common in humans despite the fact that it reduces muscle size, strength and power. Because of the close relationship between skeletal muscle function and cardiometabolic health we examined the influence of ACTN3 R577X polymorphism over cardiovascular and metabolic characteristics of young adults (n = 98 males, n = 102 females; 23 ± 4.2 years) from our Assessing Inherent Markers for Metabolic syndrome in the Young (AIMMY) ...[more]

PMID: 26107372

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Project description:BackgroundAbility of athletes in speed or endurance contests somehow is determined by inherited muscle fiber types. One of the important genes involved in sport genetics is ACTN3 that is located on chromosome 11q13-q14 and encodes α-actinin-3, which belongs to highly conserved family of α-actinin proteins. Genetic analysis of α-actinin-3 gene has showed a polymorphism R577X (rs1815739), which results in premature stop codon and leads to non functional α-actnin-3 protein. ACTN3 genotype can contribute to the performance in elite and endurance activities. R577X polymorphism replaces arginine by stop codon. Individuals homozygous for R577 have full copy of α-actinin-3 and elite and power sprint athletes show significantly higher frequency of 577R allele. In the other hand, some studies represented that X allele have high level of frequency in endurance athletes. However, this data remains controversial Since there is no information about the frequency of ACTN3 genotype in our population therefore as the first step it is essential to determine the genetic background of Iranian population. The objective of this study was to genotype normal Iranian individuals to determine the prevalence of each allele in our population.MethodsWe used PCR-RFLP method for genotyping 210 normal individuals.ResultsTotal of 210 Iranian normal individuals for distribution of R577X and R alleles were genotyped. The different genotypes were as follow; 24% RR (50/210), 65%RX (136/210) and 11%XX (24/210), with allelic distribution of 0.56 and 0.44 for 577R and 577X alleles of ACTN3.ConclusionThis allelic distribution for Iranian's is more close to Caucasian population, which is concurrent with the route of ancient human's migration from Iran Plateau toward Europe. Our results showed no different patterns of allelic distribution among female and males, which was the same in other studies too, although some differences has been reported in the studies on athletes population.

Project description:ObjectiveThe 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.MethodsMulti-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.ResultsSignificant 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.ConclusionsIn 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.

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The ACTN3 R577X Polymorphism Is Associated with Cardiometabolic Fitness in Healthy Young Adults.

Publications

The ACTN3 R577X Polymorphism Is Associated with Cardiometabolic Fitness in Healthy Young Adults.

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