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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)


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. VO2max 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 × 10–9). Furthermore, the HFE G allele was associated with high V̇O2max 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.

Original languageEnglish
Pages (from-to)665-673
Number of pages9
JournalEuropean Journal of Applied Physiology
Issue number3
Publication statusPublished - 2020 Mar 1
Externally publishedYes


  • Athletes
  • Endurance performance
  • Gene
  • Genotype
  • Hemochromatosis

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Public Health, Environmental and Occupational Health
  • Physiology (medical)


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