ACTN3 R577X and ACE I/D gene variants influence performance in elite sprinters: a multi-cohort study.

BACKGROUND: To date, studies investigating the association between ACTN3 R577X and ACE I/D gene variants and elite sprint/power performance have been limited by small cohorts from mixed sport disciplines, without quantitative measures of performance. AIM: To examine the association between these variants and sprint time in elite athletes. METHODS: We collected a total of 555 best personal 100-, 200-, and 400-m times of 346 elite sprinters in a large cohort of elite Caucasian or African origin sprinters from 10 different countries. Sprinters were genotyped for ACTN3 R577X and ACE ID variants. RESULTS: On average, male Caucasian sprinters with the ACTN3 577RR or the ACE DD genotype had faster best 200-m sprint time than their 577XX (21.19 ± 0.53 s vs. 21.86 ± 0.54 s, p = 0.016) and ACE II (21.33 ± 0.56 vs. 21.93 ± 0.67 sec, p = 0.004) counterparts and only one case of ACE II, and no cases of ACTN3 577XX, had a faster 200-m time than the 2012 London Olympics qualifying (vs. 12 qualified sprinters with 577RR or 577RX genotype). Caucasian sprinters with the ACE DD genotype had faster best 400-m sprint time than their ACE II counterparts (46.94 ± 1.19 s vs. 48.50 ± 1.07 s, p = 0.003). Using genetic models we found that the ACTN3 577R allele and ACE D allele dominant model account for 0.92 % and 1.48 % of sprint time variance, respectively. CONCLUSIONS: Despite sprint performance relying on many gene variants and environment, the % sprint time variance explained by ACE and ACTN3 is substantial at the elite level and might be the difference between a world record and only making the final.

Elite athletes' genetic predisposition for altered risk of complex metabolic traits.

BACKGROUND: Genetic variants may predispose humans to elevated risk of common metabolic morbidities such as obesity and Type 2 Diabetes (T2D). Some of these variants have also been shown to influence elite athletic performance and the response to exercise training. We compared the genotype distribution of five genetic Single Nucleotide Polymorphisms (SNPs) known to be associated with obesity and obesity co-morbidities (IGF2BP2 rs4402960, LPL rs320, LPL rs328, KCJN rs5219, and MTHFR rs1801133) between athletes (all male, n = 461; endurance athletes n = 254, sprint/power athletes n = 207), and controls (all male, n = 544) in Polish and Russian samples. We also examined the association between these SNPs and the athletes' competition level ('elite' and 'national' level). Genotypes were analysed by Single-Base Extension and Real-Time PCR. Multinomial logistic regression analyses were conducted to assess the association between genotypes and athletic status/competition level. RESULTS: IGF2BP2 rs4402960 and LPL rs320 were significantly associated with athletic status; sprint/power athletes were twice more likely to have the IGF2BP2 rs4402960 risk (T) allele compared to endurance athletes (OR = 2.11, 95% CI = 1.03-4.30, P <0.041), and non-athletic controls were significantly less likely to have the T allele compared to sprint/power athletes (OR = 0.62, 95% CI =0.43-0.89, P <0.0009). The control group was significantly more likely to have the LPL rs320 risk (G) allele compared to endurance athletes (OR = 1.26, 95% CI = 1.05-1.52, P <0.013). Hence, endurance athletes were the "protected" group being significantly (p < 0.05) less likely to have the risk allele compared to sprint/power athletes (IGF2BP2 rs4402960) and significantly (p < 0.05) less likely to have the risk allele compared to controls (LPL rs320). The other 3 SNPs did not show significant differences between the study groups. CONCLUSIONS: Male endurance athletes are less likely to have the metabolic risk alleles of IGF2BP2 rs4402960 and LPL rs320, compared to sprint/power athletes and controls, respectively. These results suggest that some SNPs across the human genome have a dual effect and may predispose endurance athletes to reduced risk of developing metabolic morbidities, whereas sprint/power athletes might be predisposed to elevated risk.

hTERT, BICD1 and chromosome 18 polymorphisms associated with telomere length affect kidney allograft function after transplantation.

BACKGROUND/AIMS: It has been confirmed that telomere length (TL) correlates with chronological donor age and that telomere shortening is accelerated in allografts. The aim of this study was to analyse the associations between graft rs2735940 hTERT and rs2630578 BICD1 gene polymorphisms and rs7235755/rs2162440 chromosome 18 polymorphisms, relative TL and kidney function after transplantation. METHODS: The study enrolled 119 Polish Caucasian kidney allograft recipients (64M/55F, mean age 47.3±14.0 years). The relative TL was assessed in biopsy specimens. To identify genotypes of the studied polymorphisms, real-time PCR was performed. RESULTS: The graft rs2735940 hTERT gene polymorphism TT genotype was associated with a significantly lower risk of delayed graft function (DGF) (TT vs. TC+CC; OR=0, p=0.009) and significantly shorter TL in the '0' biopsy (TT vs. CC: 207±153 vs. 400±161, p=0.036). The graft rs2630578 BICD1 gene polymorphism CC genotype was associated with lower creatinine concentrations in the first month (CC vs. GC: 1.11±0.06 vs. 2.0±1.25 mg/dL, p=0.03). The AA genotype of the graft rs7235755 chromosome 18 polymorphism was associated with longer relative TL in specimens collected 12 to 60 months after transplantation (AA vs. GG+GA p=0.04; AA vs. GG: 489±152 vs. 246±145, p=0.035) and the presence of A allele was associated with higher creatinine concentrations one month after transplantation (GA+AA vs. GG p=0.026; GA vs. GG: 2.18±1.59 vs. 1.76±0.88 mg/dL, p=0.02). It was found that shorter TL in the first six months was associated with higher creatinine concentrations 12 and 18 months after transplantation (Rs=-0.32; p=0.07 and Rs=-0.54; p=0.006, respectively). CONCLUSIONS: Graft rs2735940 hTERT and rs2630578 BICD1 gene polymorphisms and rs7235755/rs2162440 chromosome 18 polymorphisms, apart from the association with TL, affect early kidney function after transplantation. Relative TL correlated negatively with creatinine concentrations, allowing the use of TL as a predictor of long-term kidney function.

EPAS1 gene variants are associated with sprint/power athletic performance in two cohorts of European athletes.

BACKGROUND: The endothelial PAS domain protein 1 (EPAS1) activates genes that are involved in erythropoiesis and angiogenesis, thus favoring a better delivery of oxygen to the tissues and is a plausible candidate to influence athletic performance. Using innovative statistical methods we compared genotype distributions and interactions of EPAS1 SNPs rs1867785, rs11689011, rs895436, rs4035887 and rs1867782 between sprint/power athletes (n=338), endurance athletes (n=254), and controls (603) in Polish and Russian samples. We also examined the association between these SNPs and the athletes' competition level ('elite' and 'sub-elite' level). Genotyping was performed by either Real-Time PCR or by Single-Base Extension (SBE) method. RESULTS: In the pooled cohort of Polish and Russian athletes, 1) rs1867785 was associated with sprint/power athletic status; the AA genotype in rs1867785 was underrepresented in the sprint/power athletes, 2) rs11689011 was also associated with sprint/power athletic status; the TT genotype in rs11689011 was underrepresented sprint/power athletes, and 3) the interaction between rs1867785, rs11689011, and rs4035887 was associated with sprint/power athletic performance; the combinations of the AA genotype in rs4035887 with either the AG or GG genotypes in rs1867785, or with the CT or CC genotypes in rs11689011, were underrepresented in two cohorts of sprint/power athletes. CONCLUSIONS: Based on the unique statistical model rs1867785/rs11689011 are strong predictors of sprint/power athletic status, and the interaction between rs1867785, rs11689011, and rs4035887 might contribute to success in sprint/power athletic performance.

AGTR2 gene polymorphism is associated with muscle fibre composition, athletic status and aerobic performance.

Muscle fibre type is a heritable trait and can partly predict athletic success. It has been proposed that polymorphisms of genes involved in the regulation of muscle fibre characteristics may predispose the muscle precursor cells of a given individual to be predominantly fast or slow. In the present study, we examined the association between 15 candidate gene polymorphisms and muscle fibre type composition of the vastus lateralis muscle in 55 physically active, healthy men. We found that rs11091046 C allele carriers of the angiotensin II type 2 receptor gene (AGTR2; involved in skeletal muscle development, metabolism and circulatory homeostasis) had a significantly higher percentage of slow-twitch fibres than A allele carriers [54.2 (11.1) versus 45.2 (10.2)%; P = 0.003]. These data indicate that 15.2% of the variation in muscle fibre composition of the vastus lateralis muscle can be explained by the AGTR2 genotype. Next, we investigated the frequencies of the AGTR2 alleles in 2178 Caucasian athletes and 1220 control subjects. The frequency of the AGTR2 C allele was significantly higher in male and female endurance athletes compared with power athletes (males, 62.7 versus 51.7%, P = 0.0038; females, 56.6 versus 48.1%, P = 0.0169) and control subjects (males, 62.7 versus 51.0%, P = 0.0006; elite female athletes, 65.1 versus 55.2%, P = 0.0488). Furthermore, the frequency of the AGTR2 A allele was significantly over-represented in female power athletes (51.9%) in comparison to control subjects (44.8%, P = 0.0069). We also found that relative maximal oxygen consumption was significantly greater in male endurance athletes with the AGTR2 C allele compared with AGTR2 A allele carriers [n = 28; 62.3 (4.4) versus 57.4 (6.0) ml min(-1) kg(-1); P = 0.0197]. Taken together, these results demonstrate that the AGTR2 gene C allele is associated with an increased proportion of slow-twitch muscle fibres, endurance athlete status and aerobic performance, while the A allele is associated with a higher percentage of fast-twitch fibres and power-oriented disciplines.

Association of the MTHFR 1298A>C (rs1801131) polymorphism with speed and strength sports in Russian and Polish athletes.

It has been suggested that DNA hypomethylation because of poorer effectiveness of the 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme induces muscular growth. We hypothesised that the common, functional 1298A>C polymorphism in the MTHFR gene is associated with athletic status. To test this hypothesis, we investigated the distribution of the 1298A>C variant in Polish (n = 302) and Russian (n = 842) athletes divided into four groups: endurance, strength-endurance, sprint-strength and strength-endurance, as well as in 1540 control participants. We found different genotypes (the AC heterozygote advantage) and allele distributions among sprint-strength athletes and strength athletes than the groups of sedentary controls for each nationality. In the combined study, the allelic frequencies for the 1298C variant were 35.6% in sprint-strength athletes (OR 1.18 [1.02-1.36], P = 0.024 vs. controls) and 38.6% in strength athletes (OR 1.34 [1.10-1.64], P = 0.003 vs. controls). The results of the initial and repetition studies as well as the combined analysis suggest that the functional 1298A>C polymorphism in the MTHFR gene is associated with athletic status. The presence of the C allele seems to be beneficial in sprint-strength and strength athletes. It needs to be established whether and to what extent this effect is mediated by alteration in DNA methylation status.

The -9/+9 polymorphism of the bradykinin receptor Beta 2 gene and athlete status: a study involving two European cohorts.

Previous studies concerning the relevance of BDKRB2 gene polymorphisms revealed that the absence (-9 allele) of a nine-base-pair sequence in exon 1 of the BDKRB2 gene is correlated with higher skeletal muscle metabolic efficiency, glucose uptake during exercise, and endurance athletic performance. The aim of the study was to investigate the association between the BDKRB2 -9/+9 polymorphism and elite athletic status in two cohorts of eastern European athletes. We examined the genotype distribution of the BDKRB2 9/+9 polymorphic site in a group of Polish athletes and confirmed the results obtained in a replication study of Russian athletes. Three hundred and two Polish athletes and 684 unrelated sedentary controls, as well as 822 Russian athletes and 507 unrelated sedentary volunteers, were recruited for this study. All samples were genotyped for the -9/+9 polymorphism within exon 1 of the BDKRB2 gene using polymerase chain reaction. Significance was assessed by chi square analysis with Bonferroni's correction for multiple testing. We found no statistical difference in the -9/+9 genotype and allele frequencies in two groups of athletes divided into four subgroups: endurance, sprint-endurance, sprint-strength, and strength athletes, compared with controls. There were no significant differences in allele frequencies (p = 0.477) and genotype distribution (p = 0.278) in the initial and replication studies. Thus, no association was found between the BDKRB2 -9/+9 polymorphism and elite athletic status in two cohorts of eastern European athletes.

Association of the ADRB2 Gly16Arg and Glu27Gln polymorphisms with athlete status.

The ß-adrenergic receptors (ß-ARs) have known functional roles in cardiovascular and pulmonary responses as well as the appropriate substrate metabolism required for athletic ability. Thus, the ß-AR genes are plausible candidates for the variations observed in strength/power and endurance performance levels. The aims of the present study were to compare the frequency distribution of the ADRB2 Gly16Arg and ADRB2 Glu27Gln polymorphisms among athletes of sports with different metabolic and cardiopulmonary demands (endurance vs. strength/power) and to test the association between the Gly16Arg and Glu27Gln genotypes and athlete status. The study was performed in a group of 223 Polish athletes of the highest nationally competitive standard (123 endurance-oriented athletes and 100 strength/power athletes). Control samples were prepared from 354 unrelated, sedentary volunteers. The χ² test of independence revealed that the frequencies of the Gly16 and Glu27 alleles were significantly higher in the strength/power athletes than in the controls (69.0% vs. 59.7%; df = 1, P = 0.017 and 51% vs. 41.5%; df = 1 P = 0.017, respectively). The study showed that ADRB2 Gly16Arg and Glu27Gln markers are associated with athlete status in Polish athletes. An excess of Gly16 and Glu27 alleles and the Gly16:Glu27 haplotype observed in the strength/power athlete subgroup suggests that the Gly16 and Glu27 alleles might increase the probability of becoming a strength/power athlete rather than an endurance-oriented athlete.

Association of rs699 (M235T) polymorphism in the AGT gene with power but not endurance athlete status.

Thus far, genetic studies of the renin-angiotensin system (RAS) with respect to athletic performance or athlete status have mainly focused on the angiotensin-converting enzyme gene and its insertion/deletion polymorphism. The aim of this study was to investigate the functional rs699 (M235T) polymorphism in angiotensinogen (AGT), the second most important gene of the RAS, for association with athletic status and level of performance. The study included 123 endurance athletes and 100 power-oriented athletes, who were classified as elite or sub-elite according to competitive achievements at the international level, and 354 unrelated sedentary control subjects. The M235T genotype and allele distributions differed significantly between power and endurance athletes (p < 0.0001 and p < 0.0002, genotypes and alleles, respectively) and between power athletes and control subjects (p < 0.0001 and p < 0.0002, genotypes and alleles, respectively). The frequency of the CC genotype in the power athlete group was 2.2 times higher and 3.1 times higher than in the control and endurance groups, respectively. No difference was found in M235T allele distribution between elite and sub-elite athletes, either in power- or endurance-oriented athletes. We conclude that the CC genotype of the M235T polymorphism is overrepresented in Polish power athletes, suggesting that the AGT M235T variant is associated with power athletes' status.

CCL2 gene polymorphism is associated with post-transplant diabetes mellitus.

Post-transplant diabetes mellitus (PTDM) is a common complication after solid organ transplantation, especially in recipients treated with calcineurin inhibitors. Previous studies suggest that chronic inflammation and chemokines play an important role in the pathogenesis of diabetes. Single-nucleotide polymorphisms (SNPs) can increase or decrease transcriptional activity and can change the production of chemokines. The aim of this study was to examine the association between CCL2 and CCL5 gene polymorphisms and the development of post-transplant diabetes mellitus. The study included 315 patients who received kidney transplants and were treated with calcineurin inhibitors. Patients were divided into two subgroups: with PTDM (n=43) and without PTDM (n=272). An additive model of univariate Cox regression analysis showed that the hazard of PTDM development was significantly positively associated with the number of CCL2 rs1024611 G alleles (HR 1.65; 95%CI 1.08-2.53; p=0.021). Multivariate Cox regression analysis, taking into the account the recipient's sex, age and BMI, as well as the number of G alleles of the CCL2 rs1024611 polymorphism, revealed that this polymorphism is an independent risk factor for post-transplant diabetes. The results of our study suggest an association between the CCL2 gene rs1024611 G allele and PTDM in patients treated with tacrolimus or cyclosporine.

No Evidence of a Common DNA Variant Profile Specific to World Class Endurance Athletes.

There are strong genetic components to cardiorespiratory fitness and its response to exercise training. It would be useful to understand the differences in the genomic profile of highly trained endurance athletes of world class caliber and sedentary controls. An international consortium (GAMES) was established in order to compare elite endurance athletes and ethnicity-matched controls in a case-control study design. Genome-wide association studies were undertaken on two cohorts of elite endurance athletes and controls (GENATHLETE and Japanese endurance runners), from which a panel of 45 promising markers was identified. These markers were tested for replication in seven additional cohorts of endurance athletes and controls: from Australia, Ethiopia, Japan, Kenya, Poland, Russia and Spain. The study is based on a total of 1520 endurance athletes (835 who took part in endurance events in World Championships and/or Olympic Games) and 2760 controls. We hypothesized that world-class athletes are likely to be characterized by an even higher concentration of endurance performance alleles and we performed separate analyses on this subsample. The meta-analysis of all available studies revealed one statistically significant marker (rs558129 at GALNTL6 locus, p = 0.0002), even after correcting for multiple testing. As shown by the low heterogeneity index (I2 = 0), all eight cohorts showed the same direction of association with rs558129, even though p-values varied across the individual studies. In summary, this study did not identify a panel of genomic variants common to these elite endurance athlete groups. Since GAMES was underpowered to identify alleles with small effect sizes, some of the suggestive leads identified should be explored in expanded comparisons of world-class endurance athletes and sedentary controls and in tightly controlled exercise training studies. Such studies have the potential to illuminate the biology not only of world class endurance performance but also of compromised cardiac functions and cardiometabolic diseases.

Adiponectin and leptin gene polymorphisms in patients with post-transplant diabetes mellitus.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) is a common metabolic complication after organ transplantation and may be associated with the use of calcineurin inhibitors (tacrolimus and cyclosporine). Leptin and adiponectin are adipokines and play an important role in the regulation of insulin secretion as well as glucose and lipid metabolism. AIM: The aim of this study was to examine the association between adiponectin and leptin gene polymorphisms and development of PTDM. MATERIALS & METHODS: The study included 323 patients who received kidney transplants and were treated with calcineurin inhibitors (tacrolimus or cyclosporine). RESULTS: The association between adiponectin and leptin gene polymorphisms and PTDM was studied in three models of Cox regression analysis--additive, dominant and recessive. In these three models, the LEP rs2167270 gene polymorphism was statistically significantly associated with increased risk of PTDM. The association between the LEP rs2167270 polymorphism and PTDM was confirmed by multivariate regression analysis. CONCLUSION: The results of our study suggest an association between the leptin rs2167270 gene A allele and PTDM. Original submitted 27 February 2015; Revision submitted 22 May 2015.

MCT1 A1470T: a novel polymorphism for sprint performance?

OBJECTIVES: The A1470T polymorphism (rs1049434) in the monocarboxylate (lactate/pyruvate) transporter 1 gene (MCT1) has been suggested to influence athletic performance in the general population. We compared genotype distributions and allele frequencies of the MCT1 gene A1470T polymorphism between endurance athletes, sprint/power athletes and matched controls. We also examined the association between the MCT1 A1470T and the athletes' competition level ('elite' and 'national' level). DESIGN: The study involved endurance athletes (n=112), sprint/power athletes (n=100), and unrelated sedentary controls (n=621), all Caucasians. METHODS: Genomic DNA was extracted from buccal epithelium using a standard protocol. We conducted Fisher's exact tests and multinomial logistic regression analyses to assess the association between MCT1 genotype and athletic status/competition level. RESULTS: Sprint/power athletes were more likely than controls to possess the minor T allele (TT genotype compared to the AA [p<0.001]; TT or AT compared to the AA [p=0.007]; TT compared to both AA and AT genotypes [p<0.001]). Likewise, sprint/power athletes were more likely than endurance athletes to have the TT genotype compared to the AA (p=0.029) and the TT compared to both AA and AT genotypes (p=0.027). Furthermore, elite sprint/power athletes were more likely than national-level athletes to have the TT genotype compared to the AA (p=0.044), and more likely to have the TT genotype compared to both AA and AT genotypes (recessive model) (p=0.045). CONCLUSIONS: The MCT1 TT genotype is associated with elite sprint/power athletic status. Future studies are encouraged to replicate these findings in other elite athlete cohorts.

The Variants Within the COL5A1 Gene are Associated with Reduced Risk of Anterior Cruciate Ligament Injury in Skiers.

The purpose of this study was to examine the association of the BstUI RFLP C/T (rs 12722) and DpnII RFLP C/T (rs 13946) COL5A1 polymorphisms, individually and as haplotypes, with anterior cruciate ligament ruptures in recreational skiers. Subjects were 138 male recreational skiers with surgically diagnosed primary anterior cruciate ligament ruptures. The control group consisted of 183 apparently healthy male recreational skiers, who were without any self-reported history of ligament or tendon injury. DNA was extracted from buccal cells donated by the subjects and genotyping was carried out using real-time PCR. The genotype distributions for both polymorphisms met Hardy-Weinberg expectations in both groups. There were no significant differences in genotype distribution of allele frequencies of COL5A1 BstUI RFLP C/T and COL5A1 DpnII RFLP C/T polymorphisms between the ACL rupture and control groups. The T-T (BstUI RFLP T, DpnII RFLP T) haplotype was the most common (55.6%). The haplotype T-C was not present in any of the subjects. There was an underrepresentation tendency of the C-T haplotype in the study group compared to controls under recessive mode of inheritance. Higher frequency of the COL5A1 BstUI RFLP C/T and COL5A1DpnII RFLP C/T polymorphisms haplotype is associated with reduced risk of anterior cruciate ligament injury in a group of apparently healthy male recreational skiers.

Interactions between collagen gene variants and risk of anterior cruciate ligament rupture.

The COL5A1 and COL12A1 variants are independently associated with modulating the risk of anterior cruciate ligament (ACL) rupture in females. The objective of this study was to further investigate if COL3A1 and COL6A1 variants independently, as well as, collagen gene-gene interactions, modulate ACL rupture risk. Three hundred and thirty-three South African (SA, n = 242) and Polish (PL, n = 91) participants with diagnosed ACL ruptures and 378 controls (235 SA and 143 PL) were recruited. Participants were genotyped for COL3A1 rs1800255 G/A, COL5A1 rs12722 (T/C), COL6A1 rs35796750 (T/C) and COL12A1 rs970547 (A/G). No significant associations were identified between COL6A1 rs35796750 and COL3A1 rs1800255 genotypes and risk of ACL rupture in the SA cohort. The COL3A1 AA genotype was, however, significantly (p = 0.036) over-represented in the PL ACL group (9.9%, n = 9) when compared to the PL control (CON) group (2.8%, n = 4). Although there were genotype distribution differences between the SA and PL cohorts, the T+A-inferred pseudo-haplotype constructed from COL5A1 and COL12A1 was significantly over-represented in the female ACL group when compared to the female CON group within the SA (T+A ACL 50.5%, T+A CON 38.1%, p = 0.022), PL (T+A ACL 56.3%, T+A CON 36.3%, p = 0.029) and combined (T+A ACL 51.8%, T+A CON 37.5%, p = 0.004) cohorts. In conclusion, the novel main finding of this study was a significant interaction between the COL5A1 rs12722 T/C and COL12A1 rs970547 A/G variants and risk of ACL injury. These results highlight the importance of investigating gene-gene interactions in the aetiology of ACL ruptures in multiple independent cohorts.

The Pro12Ala Polymorphism of the Peroxisome Proliferator-Activated Receptor Gamma Gene Modifies the Association of Physical Activity and Body Mass Changes in Polish Women.

Peroxisome proliferator-activated receptor γ is a key regulator of adipogenesis, responsible for fatty acid storage and maintaining energy balance in the human body. Studies on the functional importance of the PPARG Pro12Ala polymorphic variants indicated that the observed alleles may influence body mass measurements; however, obtained results were inconsistent. We have decided to check if body mass changes observed in physically active participants will be modulated by the PPARG Pro12Ala genotype. The genotype distribution of the PPARG Pro12Ala allele was examined in a group of 201 Polish women measured for selected body mass variables before and after the completion of a 12-week training program. The results of our experiment suggest that PPARG genotype can modulate training-induced body mass measurements changes: after completion of the training program, Pro12/Pro12 homozygotes were characterised by a greater decrease of body fat mass measurements in comparison with 12Ala allele carriers. These results indicate that the PPARG 12Ala variant may impair the training-induced positive effects on body mass measurements; however, the detailed mechanism of such interaction remained unclear and observed correlation between PPARG genotype and body mass differential effects should be interpreted with caution.

ACTN3 R577X polymorphism and team-sport performance: a study involving three European cohorts.

OBJECTIVES: To determine the association between the α-actinin-3 (ACTN3) R577X polymorphism and elite team-sport athletic status in three cohorts of European team-sport athletes. DESIGN: We compared the genotype and allele frequencies of the ACTN3 R577X (rs1815739) polymorphisms between team-sport athletes (n=205), endurance athletes (n=305), sprint/power athletes (n=378), and non-athletic controls (n=568) from Poland, Russia and Spain; all participants were unrelated European men. METHODS: Genomic DNA was extracted from either buccal epithelium or peripheral blood using a standard protocol. Genotyping was performed using several methods, and the results were replicated following recent recommendations for genotype-phenotype association studies. RESULTS: Genotype distributions of all control and athletic groups met Hardy-Weinberg equilibrium (all p>0.05). Team-sport athletes were less likely to have the 577RR genotype compared to the 577XX genotype than sprint/power athletes [odds ratio: 0.58, 95% confidence interval: 0.34-0.39, p=0.045]. However, the ACTN3 R577X polymorphism was not associated with team-sports athletic status, compared to endurance athletes and non-athletic controls. Furthermore, no association was observed for any of the genotypes with respect to the level of competition (elite vs. national level). CONCLUSIONS: The ACTN3 R577X polymorphism was not associated with team-sport athletic status, compared to endurance athletes and non-athletic controls, and the observation that the 577RR genotype is overrepresented in power/sprint athletes compared with team-sport athletes needs to be confirmed in future studies.

Association between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma gene and strength athlete status.

BACKGROUND: The 12Ala allele of the Peroxisome Proliferator-Activated Receptor gamma gene (PPARG) Pro12Ala polymorphism produces a decreased binding affinity of the PPARγ2 protein, resulting in low activation of the target genes. The 12Ala allele carriers display a significantly improved insulin sensitivity that may result in better glucose utilisation in working skeletal muscles. We hypothesise that the PPARG 12Ala allele could be associated with strength athlete status in Polish athletes. METHODOLOGY: The genotype distribution of PPARG Pro12Ala was examined in 660 Polish athletes. The athletes were stratified into four subgroups: endurance, strength-endurance, sprint-strength and strength. Control samples were prepared from 684 unrelated sedentary volunteers. A χ(2) test was used to compare the PPARG Pro12Ala allele and genotype frequencies between the different groups of athletes and control subjects. Bonferroni's correction for multiple testing was applied. RESULTS: A statistically significant higher frequency of PPARG 12Ala alleles was observed in the subgroup of strength athletes performing short-term and very intense exertion characterised by predominant anaerobic energy production (13.2% vs. 7.5% in controls; P = 0.0007). CONCLUSION: The PPARG 12Ala allele may be a relevant genetic factor favouring strength abilities in professional athletes, especially in terms of insulin-dependent metabolism, a shift of the energy balance towards glucose utilisation and the development of a favourable weight-to-strength ratio.

Gene variants within the COL1A1 gene are associated with reduced anterior cruciate ligament injury in professional soccer players.

OBJECTIVES: To examine the association of the COL1A1 -1997G/T and +1245G/T polymorphisms, individually and as haplotypes, with anterior cruciate ligament ruptures in professional soccer players. DESIGN: Subjects were 91 male professional soccer players with surgically diagnosed primary anterior cruciate ligament ruptures. The control group consisted of 143 apparently healthy male professional soccer players, who were without any self-reported history of ligament or tendon injury. Both subjects and healthy controls are from the same soccer teams, of the same ethnicity (Polish, East-Europeans for ≥3 generations), a similar age category, and had a comparable level of exposure to anterior cruciate ligament injury. METHODS: Genomic DNA was extracted from the oral epithelial cells using GenElute Mammalian Genomic DNA Miniprep Kit (Sigma, Germany). All samples were genotyped using a Rotor-Gene real-time polymerase chain reaction. RESULTS: Genotype distributions for both polymorphisms met the Hardy-Weinberg expectations in both subjects and controls (p>0.05). Higher frequency of the COL1A1 G-T (-1997G/T and +1245G/T polymorphisms) haplotype was significantly associated with reduced risk for anterior cruciate ligament rupture (Hap.score -1.98, p=0.048). The TT genotype was under-represented in the anterior cruciate ligament rupture group. However, this result was not statistically significant (p=0.084 Fisher's exact test, recessive mode: TT vs GT+GG). CONCLUSIONS: Higher frequency of the COL1A1 G-T haplotype is associated with reduced risk of anterior cruciate ligament injury in a group of professional soccer players. Consequently, carrying two copies the COL1A1 G-T haplotype may be protective against anterior cruciate ligament injury.

The FTO A/T polymorphism and elite athletic performance: a study involving three groups of European athletes.

OBJECTIVE: The FTO A/T polymorphism (rs9939609) is a strong candidate to influence obesity-related traits. Elite athletes from many different sporting disciplines are characterized by low body fat. Therefore, the aim of this study was to assess whether athletic status is associated with the FTO A/T polymorphism. SUBJECTS AND METHODS: A large cohort of European Caucasians from Poland, Russia and Spain were tested to examine the association between FTO A/T polymorphism (rs9939609) and athletic status. A total of 551 athletes were divided by type of sport (endurance athletes, n = 266 vs. sprint/power athletes, n = 285) as well as by level of competition (elite-level vs. national-level). The control group consisted of 1,416 ethnically-matched, non-athletic participants, all Europeans. Multinomial logistic regression analyses were conducted to assess the association between FTO A/T genotypes and athletic status/competition level. RESULTS: There were no significantly greater/lesser odds of harbouring any type of genotype when comparing across athletic status (endurance athletes, sprint/power athletes or control participants). These effects were observed after controlling for sex and nationality. Furthermore, no significantly greater/lesser odds ratios were observed for any of the genotypes in respect to the level of competition (elite-level vs. national-level). CONCLUSION: The FTO A/T polymorphism is not associated with elite athletic status in the largest group of elite athletes studied to date. Large collaborations and data sharing between researchers, as presented here, are strongly recommended to enhance the research in the field of exercise genomics.