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

Eugenia A Boulygina, Ildus I Ahmetov, Noriyuki Fuku, Edward V Generozov, Mohamed A Elrayess, Liliya B Andryushchenko, Yuliya E Pushkareva, Eugene V Lekontsev, Dmitry A Dyatlov, Vladimir P Pushkarev, Hisashi Naito, Hiroshi Kumagai, Mizuki Takaragawa, Ekaterina A Semenova, Daniil V Popov, Motohiko Miyachi, Oleg V Borisov, Andrey K Larin, Nikolay A Kulemin, Elena S Kostryukova, Hirofumi Zempo, Haruka Murakami, Fatima Al-Khelaifi, Egor B Akimov, Eri Miyamoto-Mikami

Journal: European journal of applied physiology 2020;120(3):665-673

PMID: 31970519

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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 in 46 male Russian endurance athletes was determined using gas analysis system.

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). Furthermore, the HFE G allele was associated with high V̇O in male athletes [CC: 61.8 (6.1), CG/GG: 66.3 (7.8) ml/min/kg; P = 0.036].

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.

Address: Department of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia.; Department of Biochemistry, Kazan Federal University, Kazan, Russia.; Graduate School of Health and Sports Science, Juntendo University, Chiba, Japan.; Central Cross Country Ski Association, Madison, WI, USA.; Anti Doping Laboratory Qatar, Sports City, Doha, Qatar.; UCL-Medical School, Royal Free Campus, London, UK.; Department of Physical Activity Research, National Institutes of Biomedical Innovation, Health and Nutrition, NIBIOHN, Tokyo, Japan.; Faculty of Health and Nutrition, Tokyo Seiei College, Tokyo, Japan.; Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Bonn, Germany.; Laboratory of Exercise Physiology, Institute for Biomedical Problems of the Russian Academy of Sciences, Moscow, Russia.; Omics Technologies OpenLab, Kazan Federal University, Kazan, Russia.; Research Fellow of Japanese Society for the Promotion of Science, Tokyo, Japan.; Medical Genetic Centre "Progen", Moscow, Russia.; Moscow Center of Advanced Sport Technologies, Moscow, Russia.; Department of the Theory of Physical Culture and Biomechanics, Ural State University of Physical Culture, Chelyabinsk, Russia.; Methodical and Analytical Department, Regional Center for Sports Training, Chelyabinsk, Russia.; Research Institute of Olympic Sports, Ural State University of Physical Culture, Chelyabinsk, Russia.; Department of Pediatrics, South Ural State Medical University, Chelyabinsk, Russia.; Department of Physical Education, Plekhanov Russian University of Economics, Moscow, Russia.; Biomedical Research Center, Qatar University, Doha, Qatar.; Department of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia. [email protected].; Department of Physical Education, Plekhanov Russian University of Economics, Moscow, Russia. [email protected].; Laboratory of Molecular Genetics, Kazan State Medical University, Kazan, Russia. [email protected].; Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Byrom St, Liverpool, L3 5AF, UK. [email protected].

DOI: 10.1007/s00421-020-04306-8

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MeSH Terms: Athletes, Case-Control Studies, Hemochromatosis Protein, Humans, Physical Endurance, Polymorphism, Single Nucleotide