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Differing evolutionary histories of the ACTN3*R577X polymorphism among the major human geographic groups.

ABSTRACT: It has been proposed that the functional ACTN3*R577X polymorphism might have evolved due to selection in Eurasian human populations. To test this possibility we surveyed all available population-based data for this polymorphism and performed a comprehensive evolutionary analysis of its genetic diversity, in order to assess the action of adaptive and random mechanisms on its variation across human geographical distribution. The derived 577X allele increases in frequency with distance from Africa, reaching the highest frequencies on the American continent. Positive selection, detected by an extended haplotype homozygosisty test, was consistent only with the Eurasian data, but simulations with neutral models could not fully explain the results found in the American continent. It is possible that particularities of Native American population structure could be responsible for the observed allele frequencies, which would have resulted from a complex interaction between selective and random factors.

SUBMITTER: Amorim CE

PROVIDER: S-EPMC4338210 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Differing evolutionary histories of the ACTN3*R577X polymorphism among the major human geographic groups.

Amorim Carlos Eduardo G CE Acuña-Alonzo Victor V Salzano Francisco M FM Bortolini Maria Cátira MC Hünemeier Tábita T

PloS one 20150223 2

It has been proposed that the functional ACTN3*R577X polymorphism might have evolved due to selection in Eurasian human populations. To test this possibility we surveyed all available population-based data for this polymorphism and performed a comprehensive evolutionary analysis of its genetic diversity, in order to assess the action of adaptive and random mechanisms on its variation across human geographical distribution. The derived 577X allele increases in frequency with distance from Africa, ...[more]

PMID: 25706920

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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.

Dataset Information

Differing evolutionary histories of the ACTN3*R577X polymorphism among the major human geographic groups.

Publications

Differing evolutionary histories of the ACTN3*R577X polymorphism among the major human geographic groups.

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