Introduction The two sarcomeric a-actinin isoforms in humans, a-actinin-2 and a-actinin-3, are acting-binding proteins that constitute the predominant component of the Z-disk [15]. Besides their me- chanical role, both proteins interact with proteins involved in nu- merous signalling and metabolic pathways [10]. The pattern of expression of the two isoforms has diverged through mammali- an evolution, with a-actinin-2 being expressed in skeletal muscle fibres and cardiomyocites, while the expression of a-ac- tinin-3 is almost exclusively restricted to fast, glycolytic type II muscle fibres [10,12], which are responsible for generating force- ful contractions at high velocity [10]. Abstract The Z-disk protein a-actinin-3 is only expressed in type II muscle fibres, which are responsible for generating forceful contractions at high velocity. Despite the evolutionary conservation of a-ac- tinin-3, approximately one in every five Caucasians of European ancestry is totally deficient in this protein, due to homozygosity for a R577X polymorphism in the ACTN3 gene. This, together with the results of recent research on elite athletes, suggests that the ªnullº XX polymorphism might confer some advantage to en- durance performance events. To test this hypothesis, we studied the frequency distribution of R577X genotypes in a group of 50 top-level male professional cyclists (26.9  0.4 yrs [mean  SEM]; V Ç O 2max : 73.5  0.8 ml ´ kg ±1 ´min ±1 ). Their results were compared with those of a group of 52 Olympic-class male endurance run- ners (26.8  0.6 yrs; V Ç O 2max : 73.3  0.8 ml ´ kg ±1 ´min ±1 ) and 123 healthy, sedentary male controls. All subjects were Caucasian, and of European ancestry. No significant differences (p > 0.05) were found between groups: RR: 28.5%; RX: 53.6% and XX: 17.9% in controls; RR: 28.0%; RX: 46.0% and XX: 26.0% in cyclists; and RR: 25.0%; RX: 57.7%; XX: 17.3% in runners). No differences were found in indices of endurance performance (VO 2peak or ven- tilatory thresholds) between athlete carriers of each R577X gen- otype. In summary, although the a-actinin-3 deficient XX geno- type may be detrimental for sprint performance in humans, the R577X polymorphism of the ACTN3 gene does not appear to con- fer an advantage on the ability of male athletes to sustain ex- treme endurance performance. Keywords a-actinin-3 ´ polymorphism ´ gene ´ runners Physiology & Biochemistry 1 Affiliation 1 European University of Madrid, Madrid, Spain 2 Cooper Institute Center for Human Performance and Nutrition Research, Dallas, Texas, USA 3 Department of Physiology, Sport Medicine Center, Higher Sports Council, Madrid, Spain 4 Medical Department, Spanish Track and Field Federation, Madrid, Spain 5 Professional cycling team Isles Baleares, Baleares, Spain 6 Department of Biochemistry and Physiology, University of Valladolid, ncity?, Spain 7 Departamento de Physical Education, University of León, ncity?, Spain 8 Department of Exercise and Sport Science, University of Wisconsin-La Crosse, La Crosse, WI, USA Correspondence Alejandro Lucía, MD PhD ´ European University of Madrid ´ nStreet? ´ 28670 Madrid ´ Spain ´ Fax: 34 91616 82 65 ´ E-mail: alejandro.lucia@uem.es Accepted after revision: December 1, 2005 Bibliography Int J Sports Med 2006; 27: 1 ± 5  Georg Thieme Verlag KG ´ Stuttgart ´ New York ´ DOI 10.1055/s-2006-923862 ´ ISSN 0172-4622 A. Lucia 1 F. Gómez-Gallego 1 C. Santiago 1 F. BandrØs 1 C. Earnest 2 M. Rabadµn 3 J. M. Alonso 4 J. Hoyos 5 A. Córdova 6 G. Villa 7 C. Foster 8 ACTN3 Genotype in Professional Endurance Cyclists Zeitschrift IJSM sm456 Satzbetrieb Ziegler + Müller AK-PDF tt.mm.jj Verlag Thieme/Hentze ef-Upload tt.mm.jj Datum 10.02.2006