Genetic insights into endurance athlete status: A meta-analysis of ACVR1B, AGT, FTO, IL-6, and NRF2 gene polymorphisms

The aim of this meta-analysis was to analyze allele and genotype pattern frequencies of five different gene polymorphisms associated with endurance athlete status. Endurance sports require prolonged physical performance, and it is well known that physiological and genetic characteristics play a prominent role in this performance. In recent years, research on the impact of genetic factors on endurance athlete status has been on the rise, suggesting that various gene polymorphisms may be associated with physical performance. Specifically, the gene polymorphisms, activin receptor type-1B (<i>A9CVR1B</i>) rs2854464, angiotensinogen (<i>AGT</i>) rs699, fat mass and obesity-associated (<i>FTO</i>) rs9939609, interleukin-6 (<i>IL-6</i>) rs1800795, and nuclear factor erythroid 2 (<i>NRF2</i>) rs12594956, are thought to be related to endurance athlete status. Each of these genes plays a part in different biological processes, such as muscle development, energy metabolism, inflammation, and antioxidant defense mechanisms. For example, the <i>NRF2</i> gene is a critical player in the regulation of cellular stress responses and may contribute to adaptive responses that enhance performance in endurance athletes. This meta-analysis included a total of 20 articles published between 2009 and 2023. The specific gene polymorphisms explored in this study, i.e., <i>ACVR1B</i> rs2854464, <i>AGT</i> rs699, <i>FTO</i> rs9939609, <i>IL-6</i> rs1800795, and <i>NRF2</i> rs12594956, were selected due to their reported associations with physical performance and endurance. A comprehensive search was conducted in the Web of Science and PubMed databases using specific keywords, preliminarily identifying 329 articles. Upon analysis of the abstracts, and full texts, 20 articles were deemed eligible for inclusion in this meta-analysis. Articles lacking control and endurance athlete groups or clear allele/genotype data were excluded. The findings indicated no significant differences in allele and genotype frequencies for <i>ACVR1B</i>, <i>AGT</i>, <i>FTO</i>, and <i>IL-6</i> gene polymorphisms between endurance athletes and control groups. However, the <i>NRF2</i> rs12594956 gene polymorphism showed a significantly higher frequency of the major allele (A) and the AA genotype in endurance athletes than in controls. In conclusion, the <i>NRF2</i> rs12594956 polymorphism may be a genetic variant of interest in determining the status of endurance athletes. These findings highlight the potential clinical implications for genetic screening and personalized training programs in sport genetics. More extensive studies with larger cohorts are needed to further confirm these associations.