Association between Complex ACTN3 and ACE Gene Polymorphisms and Elite Endurance Sports in Koreans: A Case–Control Study

<i>ACTN3 R577X</i> and <i>ACE I/D</i> polymorphisms are associated with endurance exercise ability. This case-control study explored the association of <i>ACTN3</i> and <i>ACE</i> gene polymorphisms with elite pure endurance in Korean athletes, hypothesizing that individuals with both <i>ACTN3 XX</i> and <i>ACE II</i> genotypes would exhibit superior endurance. We recruited 934 elite athletes (713 males, 221 females) and selected 45 pure endurance athletes (36 males, 9 females) requiring "≥90% aerobic energy metabolism during sports events", in addition to 679 healthy non-athlete Koreans (361 males, 318 females) as controls. Genomic DNA was extracted and genotyped for <i>ACTN3 R577X</i> and <i>ACE I/D</i> polymorphisms. <i>ACE ID</i> (<i>p</i> = 0.090) and <i>ACTN3 RX</i>+<i>XX</i> (<i>p</i> = 0.029) genotype distributions were significantly different between the two groups. Complex <i>ACTN3-ACE</i> genotypes also exhibited significant differences (<i>p</i> = 0.014), with dominant complex genotypes positively affecting endurance (<i>p</i> = 0.039). The presence of <i>RX</i>+<i>II</i> or <i>XX</i>+<i>II</i> was associated with a 1.763-fold higher likelihood of possessing a superior endurance capacity than that seen in healthy controls (90% CI = 1.037-3.089). Our findings propose an association of combined <i>ACTN3 RX</i>+<i>XX</i> and <i>ACE II</i> genotypes with enhanced endurance performance in elite Korean athletes. While causality remains to be confirmed, our study highlights the potential of <i>ACTN3-ACE</i> polymorphisms in predicting elite endurance.