A Catalog of Coding Sequence Variations in Salivary Proteins' Genes Occurring during Recent Human Evolution.

Saliva houses over 2000 proteins and peptides with poorly clarified functions, including proline-rich proteins, statherin, P-B peptides, histatins, cystatins, and amylases. Their genes are poorly conserved across related species, reflecting an evolutionary adaptation. We searched the nucleotide substitutions fixed in these salivary proteins' gene loci in modern humans compared with ancient hominins. We mapped 3472 sequence variants/nucleotide substitutions in coding, noncoding, and 5'-3' untranslated regions. Despite most of the detected variations being within noncoding regions, the frequency of coding variations was far higher than the general rate found throughout the genome. Among the various missense substitutions, specific substitutions detected in PRB1 and PRB2 genes were responsible for the introduction/abrogation of consensus sequences recognized by convertase enzymes that cleave the protein precursors. Overall, these changes that occurred during the recent human evolution might have generated novel functional features and/or different expression ratios among the various components of the salivary proteome. This may have influenced the homeostasis of the oral cavity environment, possibly conditioning the eating habits of modern humans. However, fixed nucleotide changes in modern humans represented only 7.3% of all the substitutions reported in this study, and no signs of evolutionary pressure or adaptative introgression from archaic hominins were found on the tested genes.

ACTN3 R577X Polymorphism Is Associated With the Incidence and Severity of Injuries in Professional Football Players.

OBJECTIVE: The ACTN3 R577X gene variant results in the absence of the α-actinin-3 protein in ∼18% of humans worldwide and has been associated with athletic performance and increased susceptibility to eccentric muscle damage. The aim of this study was to investigate the association between ACTN3 R577X variant and indirect muscle disorders/injuries in professional football players. DESIGN: A case-control, genotype-phenotype association study. INTERVENTION: Two hundred fifty-seven male professional Italian football players (from Serie A, Primavera, Allievi, and Giovanissimi; age = 21.2 ± 5.3 years) and 265 nonathletic controls were recruited for the study. Genomic DNA was extracted using a buccal swab, and the ACTN3 R577X genotype was performed using a PCR method. Structural-mechanical injuries and functional muscle disorders were collected from a subgroup of 169 football players during the period of 2009 to 2014. MAIN OUTCOME MEASURE: We hypothesized that the 577XX genotype would be associated with higher predisposition to muscle injuries (compared with the other genotypes). RESULTS: ACTN3 XX (α-actinin-3 deficiency) players had 2.66 higher odds for an injury incidence than their ACTN3 RR counterparts (95% confidence interval [CI]: 1.09-6.63, P = 0.02), whereas RX and RR players had similar injury incidence. Furthermore, ACTN3 XX players had 2.13 higher odds for having a severe injury compared with their RR counterparts (95% CI: 1.25-3.74, P = 0.0054), whereas RX individuals had 1.63 higher odds for having a severe injury compared with the RR players (95% CI: 1.10-2.40, P = 0.015). CONCLUSIONS: The ACTN3 R577X polymorphism is associated with the incidence and severity of muscle injuries in professional football players; players with the ACTN3 577XX genotype have higher odds of having muscle injuries than their RR counterparts. CLINICAL RELEVANCE: Discovering the complex relationship between gene variants and muscle injuries may assist coaches, physiologists, and the medical community to development tailored injury prevention program for football players, which could provide a new edge for successful competition.

Association Between MCT1 A1470T Polymorphism and Fat-Free Mass in Well-Trained Young Soccer Players.

The aim of this study was to investigate the association between the MCT1 A1470T polymorphism and fat-free mass in young Italian elite soccer players. Participants were 128 Italian male soccer players. Fat-free mass was estimated for each of the soccer player using age- and gender-specific formulas with plicometry. Genotyping for the MCT1 A1470T polymorphism was performed using polymerase chain reaction. The MCT1 A1470T genotypes were in agreement with the Hardy-Weinberg equilibrium distribution. The percentage of fat-free mass was significantly higher in soccer players with the TT genotype and in the T-allele-dominant model group (TT + AT) compared with the soccer players with the AA genotype. The MCT1 T allele is associated with the percentage of fat-free mass in young elite male soccer players. Elucidating the genetic basis of body composition in athletes could potentially be used as an additional tool for strength and conditioning professionals in planning and adjusting training. However, these results are preliminary and need to be replicated in more cohorts.

Somatotype of elite Italian gymnasts.

The somatotyping method is especially helpful in sports in which the body could directly influence the biomechanics of movements and the performance's results. The purpose of this study was to determine the somatotype of elite Italian gymnasts and to compare it in terms of competition levels. The sample comprised 64 elite gymnasts (42 females (F), somatotype 1.4-4.4-3.2; and 22 males (M), somatotype 1.6-6.3-2.1) belonging to the Italian National Artistic Gymnastic Team (2007) at different competition levels: Allieve, Junior, and Senior. Mean whole somatotypes, by competition levels, were not significantly different in both sexes (Female gymnasts: Allieve, 1.3-4.6-3.3; Junior, 1.3-4.2-3.6; Senior, 1.7-4.2-2.7; Male gymnasts: Junior, 1.5-6.3-2.5; Senior, 1.7-6.3-1.6). Male Junior gymnasts exhibited greater ectomorphy than Senior athletes (F1,20 = 7.75, p < 0.01). Compared to other elite athletes male and female gymnasts tend to be less endomorphic and more mesomorphic. This study highlighted the peculiarities of the somatotype of Italian elite gymnasts and their strong homogeneity, evident also from the low values of somatotype attitudinal mean (SAM). The results emphasize the need for a specific somatotype to reach an elite level in sport and the need to integrate the somatotype analysis between the scientific instruments for selecting talent also in artistic gymnastics.

Collagen Gene Variants and Anterior Cruciate Ligament Rupture in Italian Athletes: A Preliminary Report.

Several studies have investigated the role of genetics in anterior cruciate ligament (ACL) rupture, often returning conflicting results. The present pilot study aimed to analyze the association between six Single Nucleotide Polymorphisms (SNPs) (rs1800012; rs12722; rs13946; rs240736; rs970547; and rs4870723, located on the COL1A1, COL5A1, COL12A1, and COL14A1 genes), and ACL rupture, among Italian athletes. A hypothesis-driven association study was conducted. In total, 181 male and female athletes (n = 86 injured; n = 96 non-injured) were genotyped for the prioritized variants. All polymorphisms were genotyped using PCR RFLP, with the only exception being the rs1800012 on the COL1A1 gene, which was detected using MTPA PCR. The allele frequency distribution fell within the worldwide range. Despite the evident population variability, no selective pressure signals were recorded using PBS analysis. No significant difference was detected between the cases and controls for any of the SNPs (rs1800012; rs13946; rs240736; rs970547, and rs4870723) included in the analyses (p > 0.008, Bonferroni-adjusted for multiple comparisons). Moreover, no significant differences were found when males and females were assessed separately. Further investigations based on a larger sample size are needed, in order to draw solid conclusions for the influence between collagen genes and ACL rupture.

Performance scores and standings during the 43rd Artistic Gymnastics World Championships, 2011.

Scores in artistic gymnastics are subject to changes in the rules that occur each Olympic cycle as outlined in the Code of Points, because rules influence the composition of routines and therefore performance. The aim of this study was to identify the most important routine apparatus for success in a World competition. The data were the official results for the 478 gymnasts (262 men, 216 women) who competed in the 43rd Artistic Gymnastic World Championships in 2011 in Tokyo, Japan. The factors least influenced by the technical standard of competitors were performance scores on uneven bars and balance beam for women, and those on pommel horse for men. For uneven bars, balance beam, and pommel horse, scores were consistently good predictors of final standing. Our results suggest that high scores on these apparatus have a greater influence on overall performance than scores on the other apparatus, regardless of the competitors' standard.

Worldwide variation of the COL14A1 gene is shaped by genetic drift rather than selective pressure.

BACKGROUND: The aim of this study is to analyze the worldwide distribution of SNP rs4870723 in COL14A1 gene to check if there are significant genetic differences among different populations and to test if the gene is a trait under selection. METHODS: Genomic DNA was extracted from 69 unrelated individuals from Sardinia and genotyped for SNP rs4870723. Data were compared with 26 different populations, clustered in 5 super-populations, from the public 1000 genomes database. Allele frequency and heterozygosity were calculated with Genepop. The Hardy-Weinberg equilibrium and pairwise population differentiation through analysis of molecular variance (AMOVA FST) were determined with Arlequin. RESULTS: Allele frequencies of COL14A1 rs4870723 were compared in 27 populations clustered in 5 super-populations. All populations were in the Hardy-Weinberg equilibrium. In almost all populations, allele C was the most frequent allele, reaching the highest values in East Asia. The 27 populations showed an appreciable structure, with significant differences observed between European, African, and Asian populations. CONCLUSION: Significant differences were observed in the rs4870723 SNP distribution among the populations studied. However, we found no evidence for a selective pressure. Rather, the differentiation among the populations is likely the result of founder effect, genetic drift, and cultural factors, all events known to establish and maintain genetic diversity between populations.

Selective neutrality analysis of 17 STRs in Mediterranean populations.

Detection of genes that have been targeted by natural selection is a powerful tool for predicting regions of the genome potentially linked with diseases and of interest in the field of genetic epidemiology. In recent years, several methods to detect patterns of natural selection have been developed. In general, these tests are based on different assumptions and parameters; hence, the detection of outlier loci with more than one statistical approach simultaneously will support the candidate status of a particular locus. In this study, we evaluated the presence of patterns of positive selection in 17 short tandem repeat loci genotyped in six different human populations from the Mediterranean area, for a total of 429 individuals. To identify patterns of selective pressure, we applied three different neutrality tests on the basis of different models, performing pairwise comparisons between populations. Results show the presence of one marker, a (CA)n repeat located in exon 29 of the NOS1 gene, which seems significant in the three different tests in two pairwise comparisons: Sicily vs Morocco and Balearic Islands vs Morocco. This suggests that this locus and its genome localization are candidates for further studies to investigate selective pressure, as well as for association studies.

An unexpected world population variation of MCT1 polymorphism 1470T > A involved in lactate transport.

A common missense mutation (1470T > A) in gene SLC16A1 responsible for an amino acid substitution in protein MCT1 has been associated with differential lactate transport and hence, differences in physical performance and muscle injuries in relation to physical exercise. This study describes, for the first time, the worldwide variation of MCT1 variant 1470T > A at an intra- and inter-continental level. Two thousand five hundred and four individual genotypes of 26 populations clustered in 5 population groups have been analysed with data downloaded from the public database 1000 Genomes Phase 3 Browser. Several parameters of population differentiation and structure have been explored as well as selection signatures in the whole gene. Allele T, the common variant, shows extremely high values in Sub-Saharan African groups (frequencies 86-91%) as compared with the remaining world regions (69-49%). TT genotype also predominates in African groups, showing significant differences with the rest of world populations. In view of the evidence that the TT genotype is associated with clinical implications and a better predisposition to sprint/power performances, we suggest that the high presence of the TT genotype in African populations should be taken into account in future association studies at both medical and sports fields.

ACVR1B rs2854464 Is Associated with Sprint/Power Athletic Status in a Large Cohort of Europeans but Not Brazilians.

Skeletal muscle strength and mass, major contributors to sprint/power athletic performance, are influenced by genetics. However, to date, only a handful of genetic variants have been associated with sprint/power performance. The ACVR1B A allele (rs rs2854464) has previously been associated with increased muscle-strength in non-athletic cohort. However, no follow-up and/or replications studies have since been conducted. Therefore, the aim of the present study was to compare the genotype distribution of ACVR1B rs2854464 between endurance athletes (E), sprint/power (S/P) athletes, mixed athletes (M), and non-athletic control participants in 1672 athletes (endurance athletes, n = 482; sprint/power athletes, n = 578; mixed athletes, n = 498) and 1089 controls (C) of both European Caucasians (Italian, Polish and Russians) and Brazilians. We have also compared the genotype distribution according to the athlete's level of competition (elite vs. sub-elite). DNA extraction and genotyping were performed using various methods. Fisher's exact test (adjusted for multiple comparisons) was used to test whether the genotype distribution of rs2854464 (AA, AG and GG) differs between groups. The A allele was overrepresented in S/P athletes compared with C in the Caucasian sample (adjusted p = 0.048), whereas there were no differences in genotype distribution between E athletes and C, in neither the Brazilian nor the Caucasian samples (adjusted p > 0.05). When comparing all Caucasian athletes regardless of their sporting discipline to C, we found that the A allele was overrepresented in athletes compared to C (adjusted p = 0.024). This association was even more pronounced when only elite-level athletes were considered (adjusted p = 0.00017). In conclusion, in a relatively large cohort of athletes from Europe and South America we have shown that the ACVR1B rs2854464 A allele is associated with sprint/power performance in Caucasians but not in Brazilian athletes. This reinforces the notion that phenotype-genotype associations may be ethnicity-dependent.

Vitamin D receptor gene polymorphisms and musculoskeletal injuries in professional football players.

The aim of the present study was to investigate the association between vitamin D receptor (VDR) gene polymorphisms and musculoskeletal injury (MI) in elite football players. In total, 54 male professional football players were recruited from an official Italian professional championship team between 2009 and 2013. The cohort was genotyped for the ApaI, BsmI and FokI polymorphisms and MI data were collected over four football seasons. No significant differences were identified among the genotypes in the incidence rates or severity of MI (P=0.254). In addition, no significant associations were observed between VDR polymorphisms and MI phenotypes (P=0.460). However, the results of the casewise multiple regression analysis indicated that the ApaI genotypes accounted for 18% of injury severity (P=0.002). Therefore, while the BsmI and FokI polymorphisms did not appear to be associated with the severity or incidence of MI, the ApaI genotypes may have influenced the severity of muscle injury in top-level football players.

Influence of the MCT1 rs1049434 on Indirect Muscle Disorders/Injuries in Elite Football Players.

BACKGROUND: The aim of this study was to investigate the association between MCT1 rs1049434 polymorphism and indirect muscle injuries in elite football players. One hundred and seventy-three male elite Italian football players (age = 19.2 ± 5.3 years) were recruited from a first-league football club participating at the Official National Italian Football Championship (Serie A, Primavera, Allievi, Giovanissimi). The cohort was genotyped for the MCT1 rs1049434 polymorphism, and muscle injuries data were collected during the period of 2009-2014 (five football seasons). METHODS: Genomic DNA was extracted using a buccal swab, and genotyping was performed using PCR method. Structural-mechanical injuries and functional muscle disorder were included in the acute indirect muscle injury group. RESULTS: Participants with the MCT1 AA (AA = 1.57 ± 3.07, n = 69) genotype exhibit significantly higher injury incidents compared to participants with the TT genotype (TT = 0.09 ± 0.25, n = 22, P = 0.04). CONCLUSIONS: The MCT1 rs1049434 polymorphism is associated with the incidence of muscle injuries in elite football players. We anticipate that the knowledge of athletes' genetic predisposition to sports-related injuries might aid in individualizing training programs.

ACTN3 R577X polymorphism is not associated with team sport athletic status in Italians.

BACKGROUND: The ACTN3 gene may influence performance in team sports, in which sprint action and high-speed movements, regulated by the anaerobic energy system, are crucial to the ultimate success of a match. The aim of this study was to determine the association between the ACTN3 R577X (rs1815739) polymorphism and elite team sport athletic status in Italian male athletes. METHODS: We compared the genotype and allele frequency of the ACTN3 R577X polymorphism between team sport athletes (n = 75), endurance athletes (n = 40), sprint/power athletes (n = 64), and non-athletic healthy controls (n = 192) from Italy. Genomic DNA was collected using a buccal swab. Extraction was performed according to the manufacturer's directions provided with a commercially available kit (Qiagen S.r.l., Milan, Italy). RESULTS: Team sport athletes showed a lower frequency of the 577RR genotype compared to the 577XX genotype than sprint/power athletes (p = 0.044). However, the ACTN3 R577X polymorphism was not associated with team sport athletic status compared to endurance athletes and non-athletic controls. CONCLUSIONS: Our results agree with a recent large-scale study involving athletes from Spain, Poland, and Russia. The ACTN3 R577X polymorphism was not associated with team sport athletic status compared to endurance athletes and non-athletic controls.

New genetic model for predicting phenotype traits in sports.

PURPOSE: The aim of the current study was to construct a genetic model with a new algorithm for predicting athletic-performance variability based on genetic variations. METHODS: The influence of 6 polymorphisms (ACE, ACTN-3, BDKRB2, VDR-ApaI, VDR-BsmI, and VDR-FokI) on vertical jump was studied in top-level male Italian soccer players (n = 90). First, the authors calculated the traditional total genotype score and then determined the total weighting genotype score (TWGS), which accounts for the proportion of significant phenotypic variance predicted by the polymorphisms. Genomic DNA was extracted from saliva samples using a standard protocol. Genotyping was performed using polymerase chain reaction (PCR). RESULTS: The results obtained from the new genetic model (TWGS) showed that only 3 polymorphisms entered the regression equation (ACTN-3, ACE, and BDKRB2), and these polymorphisms explained 17.68-24.24% of the vertical-jump variance. With the weighting given to each polymorphism, it may be possible to identify a polygenic profile that more accurately explains, at least in part, the individual variance of athletic-performance traits. CONCLUSIONS: This model may be used to create individualized training programs based on a player's genetic predispositions, as well as to identify athletes who need an adapted training routine to account for individual susceptibility to injury.

Association between the ACTN3 R577X polymorphism and artistic gymnastic performance in Italy.

The ACTN3 (R577X) gene encodes for a structural protein that is exclusively expressed in the Z-disc of type II muscle fibers. Homozygosis (577XX) for the stop codon in the ACTN3 polymorphism results in alpha-actinin-3 complete deficiency. Previous studies have shown low frequencies of the ACTN3 XX genotype in elite sprinters compared to the general population. This study tests 35 Italian elite gymnasts and 53 controls. ACTN3 XX genotype (2.8% vs. 18.8%; p < 0.04) and X allele (27.1% vs. 43.3%; p < 0.04) frequencies were significantly lower in gymnasts compared to controls. The ACTN3 XX genotype was underrepresented in female and male gymnasts compared to controls, but was only significant for males (male: 0% vs. 16.1%, p < 0.04; female: 5.5% vs. 22.7%, p = 0.39). These results suggest that alpha-actinin-3 is beneficial to skeletal muscle function in generating forceful contractions at high velocity. In conclusion, our results associated the ACTN3 R577X polymorphism with male and possibly female elite gymnastic performance.

Mitochondrial sequence variation in the Guahibo Amerindian population from Venezuela.

New data were obtained on mitochondrial DNA (mtDNA) from Guahibo from Venezuela, a group so far not studied using molecular data. A population sample (n = 59) was analyzed for mtDNA variation in two control-region hypervariable segments (HV1 and HV2) by sequencing. The presence or absence of a 9-bp polymorphism in the COII/tRNA(Lys) region was studied by direct amplification and electrophoretic identification. Thirty-eight variable sites were detected in regions HV1 and HV2, defining 26 mtDNA lineages; 23.7% of these were present in a single individual. The 9-bp deletion was found in 3.39% of individuals. Nucleotide and haplotype diversities were relatively high compared with other New World populations. The identified sequence haplotypes were classified into four major haplogroups (A-D) according to previous studies, with high frequencies for A (47.46%) and C (49.15%), low frequency for B (3.39%), and an absence of D.