A036: “the Champion Gene” ACTN3 and Cold Adaptation: An Environmental Regression Model and Systematic Review

Abstract

The ACTN3 R577X (rs1815739) genetic polymorphism is a significant research topic in sports genetics, with the XX genotype exhibiting a marked geographical gradient in different populations worldwide. The frequency of the XX genotype is notably higher in cold, high-latitude regions compared to tropical areas (e.g., Sweden 25%, Russia 14.2%, while Kenya 1%). These phenomena suggest that the ACTN3 R577X polymorphism may be closely related to cold adaptation. This study aims to analyze the evolutionary mechanisms, molecular regulation, and potential application of the ACTN3 R577X polymorphism in winter sports talent selection. Using the genomic database Ensemble and the WWF terrestrial ecoregion database, the distribution characteristics of ACTN3 R577X genotypes in different latitudes and temperature conditions were systematically analyzed. Linear regression analysis was employed to explore the relationship between these genotypes and cold adaptation phenotypes. Specifically, the relationships between average latitude, average temperature, and XX genotype frequency were studied. A systematic review of the potential thermogenic mechanisms of ACTN3 polymorphism was conducted based on the terms “ACTN3,” “cold tolerance,” and “cold adaptation.” Linear regression analysis showed a significant negative correlation between average latitude and temperature, with a 1-degree increase in latitude a 0.387°C decrease in temperature (R² = 0.8632). A positive correlation was found between latitude and XX genotype frequency, where each 1-degree increase in latitude resulted in a 0.307% increase in XX frequency (p = 0.00565, R²² = 0.402). These findings suggest a link between the ACTN3 R577X polymorphism and cold adaptation. Molecular studies indicate that ACTN3 deficiency promotes slow muscle fibers and activates mitochondrial biogenesis via calcium signaling, improving energy metabolism and cold tolerance. The ACTN3 XX genotype may offer a physiological advantage in cold environments by improving muscle metabolic efficiency and thermogenesis. Linear regression results confirm the correlation between latitude, temperature, and XX genotype frequency, suggesting a genetic basis for winter sports talent selection. Despite debates on genetic drift in cold adaptation, the high frequency of this genotype in high-latitude cold regions supports the cold adaptation hypothesis. Future research should explore interactions between ACTN3 and other genes (e.g., TRPM8, CPT1A) alongside environmental factors for a more comprehensive approach to talent selection