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1 Institute for Biophysical and Clinical Research into Human Movement, Department of Exercise and Sport Science, Manchester Metropolitan University, Manchester, United Kingdom
2 Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free & University College London Medical School, London, United Kingdom
3 Human Physiology Research Group, Staffordshire University, Stoke-on-Trent, United Kingdom
4 Royal Centre for Defence Medicine H.Q., Selly Oak Hospital, Selly Oak, United Kingdom
5 Olympic Medical Institute, Northwick Park Hospital, Harrow, United Kingdom
* To whom correspondence should be addressed. E-mail: s.dhamrait{at}ucl.ac.uk.
Accumulating evidence suggests that athletic performance is strongly influenced by genetic variation. One such locus of influence is the gene for Angiotensin Converting Enzyme (ACE), which exhibits a common variant (ACE I/D). ACE can drive formation of vasoconstrictor Angiotensin II but preferentially degrades vasodilator bradykinin. The ACE I allele is associated with higher kinin activity. A common gene variant in the kinin 
2 receptor (B2R) exists: the -9 as opposed to +9, allele is associated with higher receptor mRNA expression. We tested whether this variant was associated with the efficiency of muscular contraction (delta efficiency; DE) in 115 healthy men and women, or with running distance amongst 81 Olympic standard track athletes. We further sought evidence of biological interaction with ACE I/D genotype. DE was highly significantly associated with B2R genotype (23.84 ± 2.41% vs. 24.25 ± 2.81% vs. 26.05 ± 2.26% for those of +9/+9 vs. +9/-9 vs. -9/-9 genotype (n=25, 61, 29) respectively, p=0.0008 for ANOVA adjusted for sex). There was evidence for interaction with ACE I/D genotype, with individuals who were ACE II, B2R -9/-9 having the highest DE at baseline. The ACE I / B2R -9 "high kinin receptor activity" haplotype was significantly associated with endurance (predominantly aerobic) event amongst elite athletes (p=0.003). These data suggest that common genetic variation in the B2R is associated with efficiency of skeletal muscle contraction and with distance event of elite track athletes and that at least part of the associations of ACE and fitness phenotypes is through elevation of kinin activity.
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