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Bradykinin receptor gene variant and human physical performance

²Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free and University College London Medical School, London WC1E 6JF; ¹Institute for Biophysical and Clinical Research into Human Movement, Department of Exercise and Sport Science, Manchester Metropolitan University, Alsager ST7 2HL; ³Human Physiology Research Group, Sport, Health and Exercise, Staffordshire University, Stoke-on-Trent ST4 2DF; ⁴Royal Centre for Defence Medicine Headquarters, Selly Oak Hospital, Birmingham B29 6JD; and ⁵Olympic Medical Institute, Northwick Park Hospital, Middlesex HA1 3UJ, United Kingdom

Submitted 15 August 2003 ; accepted in final form 4 November 2003

Accumulating evidence suggests that athletic performance is strongly influenced by genetic variation. One such locus of influence is the gene for angiotensin-I converting enzyme (ACE), which exhibits a common variant [ACE insertion (I)/deletion (D)]. ACE can drive formation of vasoconstrictor ANG 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 among 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, and 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, with 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 among 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.

polymorphism; angiotensin-converting enzyme; skeletal muscle; elite athlete

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