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Article ; Online: The association of HFE gene H63D polymorphism with endurance athlete status and aerobic capacity: novel findings and a meta-analysis.

Semenova, Ekaterina A / Miyamoto-Mikami, Eri / Akimov, Egor B / Al-Khelaifi, Fatima / Murakami, Haruka / Zempo, Hirofumi / Kostryukova, Elena S / Kulemin, Nikolay A / Larin, Andrey K / Borisov, Oleg V / Miyachi, Motohiko / Popov, Daniil V / Boulygina, Eugenia A / Takaragawa, Mizuki / Kumagai, Hiroshi / Naito, Hisashi / Pushkarev, Vladimir P / Dyatlov, Dmitry A / Lekontsev, Eugene V /

Pushkareva, Yuliya E / Andryushchenko, Liliya B / Elrayess, Mohamed A / Generozov, Edward V / Fuku, Noriyuki / Ahmetov, Ildus I

European journal of applied physiology

2020 Volume 120, Issue 3, Page(s) 665–673

Abstract: Purpose: Iron is an important component of the oxygen-binding proteins and may be critical to optimal athletic performance. Previous studies have suggested that the G allele of C/G rare variant (rs1799945), which causes H63D amino acid replacement, in ... ...

Abstract	Purpose: Iron is an important component of the oxygen-binding proteins and may be critical to optimal athletic performance. Previous studies have suggested that the G allele of C/G rare variant (rs1799945), which causes H63D amino acid replacement, in the HFE is associated with elevated iron indexes and may give some advantage in endurance-oriented sports. The aim of the present study was to investigate the association between the HFE H63D polymorphism and elite endurance athlete status in Japanese and Russian populations, aerobic capacity and to perform a meta-analysis using current findings and three previous studies. Methods: The study involved 315 international-level endurance athletes (255 Russian and 60 Japanese) and 809 healthy controls (405 Russian and 404 Japanese). Genotyping was performed using micro-array analysis or by PCR. VO Results: The frequency of the iron-increasing CG/GG genotypes was significantly higher in Russian (38.0 vs 24.9%; OR 1.85, P = 0.0003) and Japanese (13.3 vs 5.0%; OR 2.95, P = 0.011) endurance athletes compared to ethnically matched controls. The meta-analysis using five cohorts (two French, Japanese, Spanish, and Russian; 586 athletes and 1416 controls) showed significant prevalence of the CG/GG genotypes in endurance athletes compared to controls (OR 1.96, 95% CI 1.58-2.45; P = 1.7 × 10 Conclusions: We have shown that the HFE H63D polymorphism is strongly associated with elite endurance athlete status, regardless ethnicities and aerobic capacity in Russian athletes.
MeSH term(s)	Athletes ; Case-Control Studies ; Hemochromatosis Protein/genetics ; Humans ; Physical Endurance/genetics ; Polymorphism, Single Nucleotide
Chemical Substances	HFE protein, human ; Hemochromatosis Protein
Language	English
Publishing date	2020-01-22
Publishing country	Germany
Document type	Journal Article ; Meta-Analysis
ZDB-ID	124793-1
ISSN	1439-6327 ; 1432-1025 ; 0301-5548 ; 1439-6319
ISSN (online)	1439-6327 ; 1432-1025
ISSN	0301-5548 ; 1439-6319
DOI	10.1007/s00421-020-04306-8
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Article ; Online: ACVR1B rs2854464 Is Associated with Sprint/Power Athletic Status in a Large Cohort of Europeans but Not Brazilians.

Voisin, Sarah / Guilherme, João Paulo F L / Yan, Xu / Pushkarev, Vladimir P / Cieszczyk, Pawel / Massidda, Myosotis / Calò, Carla M / Dyatlov, Dmitry A / Kolupaev, Vitaliy A / Pushkareva, Yuliya E / Maciejewska, Agnieszka / Sawczuk, Marek / Lancha, Antonio H / Artioli, Guilherme G / Eynon, Nir

PloS one

2016 Volume 11, Issue 6, Page(s) e0156316

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Activin Receptors, Type I/genetics ; Athletes ; Athletic Performance ; Brazil ; European Continental Ancestry Group ; Female ; Gene Frequency ; Genetic Association Studies ; Humans ; Male ; Muscle Strength/genetics ; Physical Endurance/genetics ; Poland ; Polymorphism, Single Nucleotide ; Russia ; South America
Chemical Substances	ACVR1B protein, human (EC 2.7.11.30) ; Activin Receptors, Type I (EC 2.7.11.30)
Language	English
Publishing date	2016-06-02
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0156316
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Article ; Online: EPAS1 gene variants are associated with sprint/power athletic performance in two cohorts of European athletes.

Voisin, Sarah / Cieszczyk, Pawel / Pushkarev, Vladimir P / Dyatlov, Dmitry A / Vashlyayev, Boris F / Shumaylov, Vladimir A / Maciejewska-Karlowska, Agnieszka / Sawczuk, Marek / Skuza, Lidia / Jastrzebski, Zbigniew / Bishop, David J / Eynon, Nir

BMC genomics

2014 Volume 15, Page(s) 382

Abstract: 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 ...

Abstract	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.
MeSH term(s)	Adult ; Alleles ; Athletes ; Athletic Performance ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Cohort Studies ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Polymorphism, Single Nucleotide ; White People/genetics
Chemical Substances	Basic Helix-Loop-Helix Transcription Factors ; endothelial PAS domain-containing protein 1 (1B37H0967P)
Language	English
Publishing date	2014-05-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2041499-7
ISSN	1471-2164 ; 1471-2164
ISSN (online)	1471-2164
ISSN	1471-2164
DOI	10.1186/1471-2164-15-382
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Article ; Online: Elite athletes' genetic predisposition for altered risk of complex metabolic traits.

Banting, Lauren K / Pushkarev, Vladimir P / Cieszczyk, Pawel / Zarebska, Aleksandra / Maciejewska-Karlowska, Agnieszka / Sawczuk, M-Arek / Leońska-Duniec, Agata / Dyatlov, Dmitry A / Orekhov, Evgeniy F / Degtyarev, Aleksandr V / Pushkareva, Yuliya E / Yan, Xu / Birk, Ruth / Eynon, Nir

BMC genomics

2015 Volume 16, Page(s) 25

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Adult ; Alleles ; Athletes ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/pathology ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Lipoprotein Lipase/genetics ; Male ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics ; Obesity/genetics ; Obesity/pathology ; Odds Ratio ; Phenotype ; Polymorphism, Single Nucleotide ; RNA-Binding Proteins/genetics ; Risk ; Young Adult
Chemical Substances	IGF2BP2 protein, human ; RNA-Binding Proteins ; MTHFR protein, human (EC 1.5.1.20) ; Methylenetetrahydrofolate Reductase (NADPH2) (EC 1.5.1.20) ; LPL protein, human (EC 3.1.1.34) ; Lipoprotein Lipase (EC 3.1.1.34)
Language	English
Publishing date	2015-01-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2041499-7
ISSN	1471-2164 ; 1471-2164
ISSN (online)	1471-2164
ISSN	1471-2164
DOI	10.1186/s12864-014-1199-0
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Article ; Online: The ACTN3 R577X polymorphism across three groups of elite male European athletes.

Eynon, Nir / Ruiz, Jonatan R / Femia, Pedro / Pushkarev, Vladimir P / Cieszczyk, Pawel / Maciejewska-Karlowska, Agnieszka / Sawczuk, Marek / Dyatlov, Dmitry A / Lekontsev, Evgeny V / Kulikov, Leonid M / Birk, Ruth / Bishop, David J / Lucia, Alejandro

PloS one

2012 Volume 7, Issue 8, Page(s) e43132

Abstract: The ACTN3 R577X polymorphism (rs1815739) is a strong candidate to influence elite athletic performance. Yet, controversy exists in the literature owing to between-studies differences in the ethnic background and sample size of the cohorts, the latter ... ...

Abstract	The ACTN3 R577X polymorphism (rs1815739) is a strong candidate to influence elite athletic performance. Yet, controversy exists in the literature owing to between-studies differences in the ethnic background and sample size of the cohorts, the latter being usually low, which makes comparisons difficult. In this case:control genetic study we determined the association between elite athletic status and the ACTN3 R577X polymorphism within three cohorts of European Caucasian men, i.e. Spanish, Polish and Russian [633 cases (278 elite endurance and 355 power athletes), and 808 non-athletic controls]. The odds ratio (OR) of a power athlete harbouring the XX versus the RR genotype compared with sedentary controls was 0.54 [95% confidence interval (CI): 0.34-0.48; P=0.006]. We also observed that the OR of an endurance athlete having the XX versus the RR genotype compared with power athletes was 1.88 (95%CI: 1.07-3.31; P=0.028). In endurance athletes, the OR of a "world-class" competitor having the XX genotype versus the RR+RX genotype was 3.74 (95%CI: 1.08-12.94; P=0.038) compared with those of a lower ("national") competition level. No association (P>0.1) was noted between the ACTN3 R577X polymorphism and competition level (world-class versus national-level) in power athletes. Our data provide comprehensive support for the influence of the ACTN3 R577X polymorphism on elite athletic performance.
MeSH term(s)	Actinin/genetics ; Adult ; Athletes ; Athletic Performance/physiology ; European Continental Ancestry Group ; Humans ; Male ; Polymorphism, Genetic/genetics ; Young Adult
Chemical Substances	ACTN3 protein, human ; Actinin (11003-00-2)
Language	English
Publishing date	2012-08-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0043132
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Article ; Online: ACTN3 R577X polymorphism and team-sport performance: a study involving three European cohorts.

Eynon, Nir / Banting, Lauren K / Ruiz, Jonatan R / Cieszczyk, Pawel / Dyatlov, Dmitry A / Maciejewska-Karlowska, Agnieszka / Sawczuk, Marek / Pushkarev, Vladimir P / Kulikov, Leonid M / Pushkarev, Evgeny D / Femia, Pedro / Stepto, Nigel K / Bishop, David J / Lucia, Alejandro

Journal of science and medicine in sport

2014 Volume 17, Issue 1, Page(s) 102–106

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Actinin/genetics ; Adult ; Athletes/statistics & numerical data ; Athletic Performance/physiology ; Case-Control Studies ; Cohort Studies ; Europe ; Humans ; Male ; Polymorphism, Genetic ; Young Adult
Chemical Substances	ACTN3 protein, human ; Actinin (11003-00-2)
Language	English
Publishing date	2014-01
Publishing country	Australia
Document type	Comparative Study ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	1437829-2
ISSN	1878-1861 ; 1440-2440
ISSN (online)	1878-1861
ISSN	1440-2440
DOI	10.1016/j.jsams.2013.02.005
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Article ; Online: ACTN3 R577X and ACE I/D gene variants influence performance in elite sprinters: a multi-cohort study.

Papadimitriou, Ioannis D / Lucia, Alejandro / Pitsiladis, Yannis P / Pushkarev, Vladimir P / Dyatlov, Dmitry A / Orekhov, Evgeniy F / Artioli, Guilherme G / Guilherme, João Paulo L F / Lancha, Antonio H / Ginevičienė, Valentina / Cieszczyk, Pawel / Maciejewska-Karlowska, Agnieszka / Sawczuk, Marek / Muniesa, Carlos A / Kouvatsi, Anastasia / Massidda, Myosotis / Calò, Carla Maria / Garton, Fleur / Houweling, Peter J /

Wang, Guan / Austin, Krista / Druzhevskaya, Anastasiya M / Astratenkova, Irina V / Ahmetov, Ildus I / Bishop, David J / North, Kathryn N / Eynon, Nir

BMC genomics

2016 Volume 17, Page(s) 285

Abstract: 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.: ...

Abstract	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.
MeSH term(s)	Actinin/genetics ; African Continental Ancestry Group ; Alleles ; Athletes ; Athletic Performance ; Cohort Studies ; European Continental Ancestry Group ; Female ; Genotype ; Humans ; Male ; Peptidyl-Dipeptidase A/genetics ; Polymorphism, Genetic ; Running
Chemical Substances	ACTN3 protein, human ; Actinin (11003-00-2) ; ACE protein, human (EC 3.4.15.1) ; Peptidyl-Dipeptidase A (EC 3.4.15.1)
Language	English
Publishing date	2016-04-13
Publishing country	England
Document type	Journal Article
ISSN	1471-2164
ISSN (online)	1471-2164
DOI	10.1186/s12864-016-2462-3
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Article ; Online: The association of HFE gene H63D polymorphism with endurance athlete status and aerobic capacity: novel findings and a meta-analysis.

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

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

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Article ; Online: Elite athletes' genetic predisposition for altered risk of complex metabolic traits.

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Article ; Online: The ACTN3 R577X polymorphism across three groups of elite male European athletes.

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

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

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