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Bradykinin receptor gene variant and human physical performance

Williams, Alun G. and Dhamrait, Sukhbir S. and Wootton, Peter T.E. and Day, Stephen H. and Hawe, Emma and Payne, John R. and Myerson, Saul G. and World, Michael and Budgett, Richard and Humphries, Steven E. and Montgomery, Hugh E. (2004) Bradykinin receptor gene variant and human physical performance. ISSN 8750-7587

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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.

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