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See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/40687707 ACTN3 and ACE genotypes in elite Jamaican and US sprinters Article in Medicine and science in sports and exercise · January 2010 DOI: 10.1249/MSS.0b013e3181ae2bc0 · Source: PubMed CITATIONS READS 64 2,414 13 authors, including:
  See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/40687707 ACTN3 and ACE genotypes in elite Jamaican andUS sprinters  Article   in  Medicine and science in sports and exercise · January 2010 DOI: 10.1249/MSS.0b013e3181ae2bc0 · Source: PubMed CITATIONS 64 READS 2,414 13 authors , including: Some of the authors of this publication are also working on these related projects: Part of my PhD Thesis   View projectMolecular Genetic Characteristics of Elite Rugby Athletes (RugbyGene project)   View projectRachael IrvingThe University of the West Indies at Mona 41   PUBLICATIONS   294   CITATIONS   SEE PROFILE Errol Y St A MorrisonUniversity of Technology, Jamaica 33   PUBLICATIONS   495   CITATIONS   SEE PROFILE Dawn M. TladiUniversity of Botswana 4   PUBLICATIONS   68   CITATIONS   SEE PROFILE  Yannis PitsiladisUniversity of Brighton 244   PUBLICATIONS   3,314   CITATIONS   SEE PROFILE All content following this page was uploaded by  Yannis Pitsiladis on 06 January 2015. The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the srcinal documentand are linked to publications on ResearchGate, letting you access and read them immediately.  Copyright @ 200 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited. 9  ACTN3  and  ACE   Genotypes in Elite Jamaicanand US Sprinters ROBERT A. SCOTT 1 , RACHAEL IRVING 2 , LAURA IRWIN 1 , ERROL MORRISON 3 , VILMA CHARLTON 2 ,KRISTA AUSTIN 4 , DAWN TLADI 5 , MICHAEL DEASON 1 , SAMUEL A. HEADLEY 6 , FRED W. KOLKHORST 7 , NAN YANG 8 , KATHRYN NORTH 8 , and YANNIS P. PITSILADIS 1 1 University of Glasgow, Glasgow, UNITED KINGDOM;  2 University of West Indies Kingston, JAMAICA;  3 University of  Technology, Kingston, JAMAICA;  4 United States Olympic Committee, Colorado Springs, CO;  5 Georgia Southwestern StateUniversity, Americus, GA;  6  Springfield College, Springfield, MA;  7  San Diego State University, San Diego, CA;and   8  Institute for Neuromuscular Research, Children’s Hospital at Westmead, Sydney, AUSTRALIA ABSTRACT SCOTT, R. A., R. IRVING, L. IRWIN, E. MORRISON, V. CHARLTON, K. AUSTIN, D. TLADI, M. DEASON, S. A. HEADLEY,F. W. KOLKHORST, N. YANG, K. NORTH, and Y. P. PITSILADIS.  ACTN3  and  ACE   Genotypes in Elite Jamaican and US Sprinters.  Med. Sci. Sports Exerc. , Vol. 42, No. 1, pp. 107–112, 2010. The angiotensin-converting enzyme (  ACE  ) and the  > -actinin-3 (  ACTN3 )genes are two of the most studied ‘‘performance genes’’ and both have been associated with sprint/power phenotypes and elite performance.  Purpose : To investigate the association between the  ACE   and the  ACTN3  genotypes and sprint athlete status in eliteJamaican and US African American sprinters.  Methods : The  ACTN3  R577X and the  ACE   I/D and A22982G (rs4363) genotypedistributions of elite Jamaican (J-A;  N   = 116) and US sprinters (US-A;  N   = 114) were compared with controls from the Jamaican(J-C;  N   = 311) and US African American (US-C;  N   = 191) populations. Frequency differences between groups were assessed by exact test.  Results : For   ACTN3 , the XX genotype was found to be at very low frequency in both athlete and control cohorts (J-C = 2%,J-A = 3%, US-C = 4%, US-A = 2%). Athletes did not differ from controls in  ACTN3  genotype distribution (J,  P   = 0.87; US,  P =  0.58).Similarly, neither US nor Jamaican athletes differed from controls in genotype at   ACE   I/D (J,  P =  0.44; US,  P   = 0.37). Jamaicanathletes did not differ from controls for A22982G genotype (  P   = 0.28), although US sprinters did (  P   = 0.029), displaying an excess of heterozygotes relative to controls but no excess of GG homozygotes (US-C = 22%, US-A = 18%).  Conclusions : Given that   ACTN3  XXgenotype is negatively associated with elite sprint athlete status, the underlying low frequency in these populations eliminates the possibility of replicating this association in Jamaican and US African American sprinters. The finding of no excess in  ACE   DD or GGgenotypes in elite sprint athletes relative to controls suggests that   ACE   genotype is not a determinant of elite sprint athlete status. Key Words:  GENETICS, AFRICAN, ATHLETE, SPRINT, POWER  T he recent Beijing Olympics was a phenomenalsuccess for Jamaican sprinters, where they won 7of the 12 available medals in the men’s andwomen’s 100- and 200-m events as well as medals in the400-m and the sprint relays. The United States took four of the five remaining medals. This, of course, promptsquestions over why these athletes were so successful rel-ative to those of other nations. Although training andenvironmental factors are certainly acknowledged as keycomponents, there remains a belief that there is a geneticcomponent to their success. However, no genetic studieshave been undertaken in sprint athletes of this standard todate. Elite athletic performance is a complex phenotypedetermined by several environmental factors such as diet, physical training, and sociocultural factors (19). Early fam-ily studies indicated that genetic factors may also contributeto the interindividual differences in athletic performance(3,15), and a recent review has identified in excess of 200gene variants associated with fitness-related phenotypes (4),although few of these variants have been associated withelite-level athletic performance.Variants in the angiotensin-converting enzyme (  ACE  )gene have been associated with elite-level performance. Themost frequently studied variant in the  ACE   gene is the I/D polymorphism: a 287-bp Alu insert into intron 16 of thegene. Generally, the D allele is associated with power  phenotypes (20,21,37) and the I allele with endurance performance (2,7,13,20,21,30) in Caucasian populations,although findings have been equivocal (25,35). In addition, positive findings have not been replicated in other ethnicgroups because a large study of east African distancerunners did not find any association between  ACE   genotypeand elite endurance athlete status (31). In Caucasians, the I/D polymorphism has been estimated to explain up to 47% of the variance in circulating ACE levels (28), with the I allele Address for correspondence: Yannis P. Pitsiladis, Ph.D., Integrative andSystems Biology, Faculty of Biomedical and Life Sciences (IBLS),University of Glasgow, Glasgow G12 8QQ, United Kingdom; E-mail:Y.Pitsiladis@bio.gla.ac.uk.Submitted for publication January 2009.Accepted for publication May 2009.0195-9131/10/4201-0107/0MEDICINE & SCIENCE IN SPORTS & EXERCISE  Copyright     2009 by the American College of Sports MedicineDOI: 10.1249/MSS.0b013e3181ae2bc0 107  B  A  S  I     C  S   C I    E  N  C E   S    Copyright @ 200 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited. 9  being associated with lower plasma and tissue ACE levelsthan the D allele (2,9,28,38). In contrast, studies in African populations have shown that other variants of the  ACE   geneare more closely associated with circulating ACE levelsthan the I/D polymorphism (8,31,41,42). An A to Gtransition at nucleotide 22982 (rs4363), in the sequenceAF118569 (27) or 31958 as in Cox et al. (8), elicits thelargest intergenotype differences in ACE levels in bothAfro-Caribbean and European subjects (42). Although ab-solute linkage disequilibrium between I/D and A22982Ghas been shown for Caucasian populations (33), this is not the case in individuals of African descent. The I allele at I/Dhas been shown to be in linkage disequilibrium with theA allele at A22982G and the D allele with the G allele,respectively (33). Consequently, the A allele has been as-sociated with lower circulating ACE levels than the G allele(8,28). The variant at A22982G has been suggested to bea potential functional variant because of the proximity to a splice site (42), which may be influential in the produc-tion of alternative splice forms (34). Therefore, in individ-uals of African descent, the  ACE   A22982G polymorphismis potentially a better candidate for study than the  ACE   ID. > -Actinin-3 is an actin-binding protein and a keycomponent of the sarcomeric Z-line in skeletal muscle.Homozygosity for the common nonsense polymorphismR577X in the  > -actinin-3 (  ACTN3 ) gene results in defi-ciency of   > -actinin-3 in a large proportion of the global population (23). This polymorphism does not appear toresult in pathology, although muscle function does appear to be influenced by this polymorphism (5,6,10,18,36).Furthermore, a strong association has been found betweenthe  ACTN3  R577X polymorphism and the elite athletic performance in Caucasian populations (1,11,22,24,29,39).The XX genotype was found at a lower frequency in eliteAustralian sprint/power athletes relative to controls (39),which has been replicated in Finnish (22), Greek (24), andRussian athletes (1). Although a previous study of Africanathletes found no frequency differences between elite Nigerian sprinters and controls (40), the effect of   ACTN3 R577X genotypes in African athletic sprint performance isnot yet well elucidated. Previous studies have suggestedthat in US African Americans, the frequency of the XXgenotype is low (17,29), although these have been variablein other, albeit small, studies (5). This is presumed to be dueto unmeasured admixture with European Americans.African American and Jamaican sprinters of Africandescent represent the highest level of sprinting performance,yet the extent to which candidate genes for human performance influence their elite status has not yet beeninvestigated. In the present study, therefore, we investigatedthe frequency of   ACE   genotypes at   ACE   ID, A22982G, andalso  ACTN3  R577X genotypes in elite Jamaican sprint athletes and controls and in elite African American sprint athletes and controls. This allowed us to investigate theinfluence of these key performance genes on the success of the most successful sprint athletes in world athletics. METHODS All subjects provided written informed consent to participate in the study, which was approved by theUHWI/UWI/FMS Ethics Committee, University of West Indies in Jamaica, and by participating institutions in theUnited States. The Jamaican cohorts comprised 311 controlsubjects (male = 156, female = 155) from throughout theisland and 116 athletes (male = 60, female = 56) who had participated in sprint events up to 400 m, in jump events,and in throw events (100–200 m,  n  = 71; 400 m,  n  = 35; jump and throw,  n  = 10). Athletes could be subdividedfurther into categories defined by their level of perfor-mance: national-level athletes ( n  = 28), who were compet-itive at national-level competition in Jamaica and theCaribbean, and international-level athletes ( n  = 86), whohad competed at major international competition for Jamaica. Forty-six of these international athletes had wonmedals at major international competition or held sprint world records. In addition, 305 samples were collected inthe United States. They included 114 elite sprint athletes(male = 62, female = 52) who had competed in sprint eventsup to 400 m and in jump events, 109 of whom had com- peted internationally (100–200 m,  n  = 48; 400 m,  n  = 42; jump and throw,  n  = 24). One hundred and ninety-onecontrol subjects (male = 72, female = 119) were collectedfrom throughout the United States: 44 were collected fromsouthwest United States (San Diego State University, Calif),73 from the northeast United States (Springfield College,MA), and 74 from the southeast United States (Florida StateUniversity, Florida Agricultural and Mechanical University,and Georgia Southwestern University). All US subjectswere self-classified as at least 50% African American, andcontrols had not been competitive athletes.DNA samples were obtained by buccal swab andextracted as previously described (32). Samples weregenotyped for the R577X polymorphism using an RFLPmethod (18) and for the  ACE   I/D and A22982G (rs4363) as previously described (31). Genotyping success rates for   ACTN3 ,  ACE   I/D, and A22982G were 99%, 97%, and 90%,respectively. Twenty percent of the  ACTN3  assays werealso genotyped by Taqman (Applied Biosystems, Foster City, CA) in a different laboratory with 98.5% concurrence.Ten percent of both ACE assays were repeated with 100%concurrence. Subjects were tested at both loci for theHardy–Weinberg equilibrium, and all groups were found to be in accordance with the principle. Intergroup genotypefrequency differences were tested by exact tests of popu-lation differentiation (26), using Arlequin v3.01 (12). Com- parisons were made between athletes and controls in their entirety and were also separated by gender. RESULTS  ACTN3 .  ACTN3  genotype frequencies of Jamaican andAmerican subjects are shown in Table 1. As can be seen http://www.acsm-msse.org 108  Official Journal of the American College of Sports Medicine        B      A       S      I       C       S       C      I      E      N       C      E       S  Copyright @ 200 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited. 9 from Table 1, all subject groups displayed a very lowfrequency of XX genotypes. Jamaican athletes did not differ from control subjects in their   ACTN3  genotype distribution(  P   = 0.81). When only the international Jamaican athleteswere compared with controls, no differences were present (  P   = 0.74). In fact, 2 of these 46 athletes were homozygousfor the 577X allele. No frequency differences becameapparent when Jamaican athletes and controls were sepa-rated by gender (male,  P   = 0.49; female,  P   = 0.84).Similarly, US sprint athletes (US-A) did not differ in their distribution of   ACTN3  genotypes from controls (US-C;  P   = 0.63; Table 1). Again, no differences became apparent when US subjects were separated by gender (male,  P   = 0.88;female,  P   = 0.45).  ACE   A22982G and ID.  In Jamaican subjects, there wasno significant difference between athletes and controls for genotype at   ACE   A22982G (  P   = 0.30; Table 2). Male(  P   = 0.76) and female subjects (  P   = 0.28) did not differ from respective controls. Furthermore,  ACE   I/D genotypefrequencies were not different between Jamaican athletesand controls (  P   = 0.42; Table 3) nor between male (  P   = 0.73)and female (  P   = 0.57) subgroups. As can be seen fromTables 2 and 3, GG and DD genotype frequencies weresimilar between groups. Linkage disequilibrium between thetwo loci was not complete in Jamaican subjects (  D  = 0.07and  D ¶  = 0.43).US sprint athletes differed from controls in their   ACE  A22982G genotype frequency (  P   = 0.018), with anapparent excess of heterozygotes in athletes relative tocontrols (58% vs 42%; Table 2). When separated by gender,male sprint athletes also differed from controls, again withan excess of heterozygotes (  P   = 0.038; 59% vs 39%), but females did not (  P   = 0.15). US athletes did not differ significantly from controls in their   ACE   I/D genotypedistribution (  P   = 0.40; Table 3). Female athletes did not differ from controls (  P   = 0.22). Male athletes did differ from controls (  P   = 0.013), with sprinters displaying a higher frequency of DD genotypes than controls (US-A = 36%,US-C = 15%). However, this difference may be a reflectionof a lower frequency of DD genotypes among the US malecontrols because combined US controls had 31% DDgenotypes and Jamaican controls had 36% (Table 3).Jamaican controls did not differ from US controls(  P   = 0.51). Although the effects of population stratificationcannot be ruled out, neither of these three loci differedsignificantly between the three control regions of the UnitedStates (  ACTN3 ,  P   = 0.67;  ACE I/D ,  P   = 0.23;  ACE  A22982G  ,  P   = 0.13; Tables 1–3), suggesting that populationstratification was not an obvious mediator of these findings.Linkage disequilibrium between the two loci was not complete in US subjects (  D  = 0.12 and  D ¶  = 0.67). DISCUSSION The present study did not find any differences betweenJamaican or US athletes and controls for   ACTN3  genotypefrequency. However, because of the low underlyingfrequency of the  ACTN3  XX genotypes in the control populations, it would have been very difficult to haveobserved a statistically higher frequency. Jamaican sprint athletes did not differ from controls in either   ACE   I/D(  P   = 0.42) or A22982G genotype (  P   = 0.30). However, USsprint athletes differed from controls in A22982G genotypefrequency, in that they had a higher frequency of hetero-zygotes than controls (58% vs 42%) but no excess of GGgenotypes. Male US sprinters differed from male controlsfor   ACE   I/D genotype (  P   = 0.013), having a higher frequency of DD genotypes than controls (US-A = 36%,US-C = 15%). However, the frequencies shown in Table 3suggest that this may be due to a lower frequency of DD genotypes in US male controls relative to other groups.The low underlying frequency of the  ACTN3  XXgenotype in the Jamaican population is in line with previousfindings in populations of African descent (17,40). How-ever, previous workin African Americans suggested a higher  TABLE 1. Genotype frequencies of  ACTN3   R577X polymorphism. Genotype Frequency, n   (%)Allele Frequency, n   (%)Subjects RR RX XX  N   R X JamaicanControls 232 (75) 73 (23) 6 (2) 311 537 (86) 85 (14)Athletes 86 (75) 25 (22) 3 (3) 114 197 (86) 31 (14)US African AmericanControls 126 (66) 57 (30) 7 (4) 190 309 (81) 71 (19)Southwest 26 (59) 15 (34) 3 (7) 44 67 (76) 21 (24)Northeast 50 (69) 20 (28) 2 (3) 72 120 (83) 24 (17)Southeast 50 (68) 22 (30) 2 (2) 74 122 (82) 26 (18)Athletes 79 (70) 32 (28) 2 (2) 113 190 (84) 36 (16)TABLE 2. Genotype frequencies of  ACE   A22982G polymorphism. Genotype Frequency, n   (%)Allele Frequency, n   (%)Subjects AA AG GG  N   A G JamaicanControls 112 (40) 124 (44) 47 (17) 283 348 (62) 218 (38)Athletes 37 (34) 58 (53) 15 (14) 110 132 (60) 88 (40)US African AmericanControls 66 (37) 75 (42) 39 (22) 180 207 (58) 153 (43)Southwest 11 (26) 17 (41) 14 (33) 42 39 (46) 45 (54)Northeast 25 (37) 30 (44) 13 (19) 68 80 (59) 56 (41)Southeast 30 (43) 28 (40) 12 (17) 70 88 (63) 52 (37)Athletes 21 (24) 52 (58) 16 (18) 89 94 (53) 84 (47)US athletes differed significantly from controls ( P   = 0.018), showing an excess ofheterozygotes.TABLE 3. Genotype frequencies of  ACE   ID polymorphism. Genotype Frequency, n   (%)Allele Frequency, n   (%)Subjects II ID DD  N   I D JamaicanControls 53 (17) 143 (47) 108 (36) 304 249 (44) 359 (51)Athletes 21 (19) 56 (52) 31 (29) 108 98 (45) 118 (55)US African AmericanControls 32 (17) 99 (52) 59 (31) 190 163 (43) 217 (57)Southwest 2 (5) 25 (57) 17 (39) 44 29 (33) 59 (67)Northeast 13 (19) 38 (53) 21 (29) 72 64 (44) 80 (56)Southeast 17 (23) 36 (49) 21 (28) 74 70 (47) 78 (53)Athletes 12 (11) 62 (57) 36 (32) 110 86 (39) 134 (61)  ACE   AND  ACTN3  GENOTYPES OF ELITE SPRINTERS Medicine & Science in Sports & Exercise d  109  B  A  S  I     C  S   C I    E  N  C E   S  
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