Bradykinin receptor gene variant and human physical performance

Abstract

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 beta(2) receptor (B(2)R) 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 B(2)R 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 B(2)R -9/-9 having the highest DE at baseline. The ACE I/B(2)R -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 B(2)R 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.

The Kallikrein-Kinin System: Current and Future Pharmacological Targets

“…Subjects with B2R +9 / +9 genotype showed less left ventricular mass regression compared with other genotypes. B2R (+9 / −9) polymorphism was also shown to be significantly associated with higher skeletal muscle metabolic efficiency and with endurance in athletic performance (257).…”

Adrenergic-β2 receptor polymorphism and athletic performance

“…8,12 The abnormal function of the b-receptor is related to numerous diseases affecting the heart, lungs and vessels, such as heart failure, asthma and hypertension. 13 This implies that knowledge of the specific phenotypes that are altered because of single-nucleotide polymorphism allows for understanding the abnormal function of the b-receptor, and thus determines the physiological effects during physical exertion.…”

Polimorfismos genéticos determinantes da performance física em atletas de elite

“…Bradykinin is a peptide of vasodilation action and inhibitor of the cellular growth. In addition, it promotes its effect by action in specific B 1 R and B 2 R receptors (43) . The ACE gene (21 Kbp) is located in the chromosome 17 q23 and is composed of 26 exons (42) .…”

“…If the ACE plays an important role in the bradykinin metabolism, it would be reasonable to associate that the its levels present an inverse relationship with the I/D ACE polymorphism, that is, high concentrations of ACE (associated with the D allele) are linked with reduced levels of bradykinin, while low concentrations of ACE (associated with the I allele) are linked with high levels of bradykinin. To put it shortly, the bradykinin levels are dependent on the ACE genotypes and can influence both glucose pick up and muscular blood flow (58) , while it prevents the growth of the left ventricle (LV) via activation of the receptors β 2 (B 2 R) for bradykinin (43,59) . A variant in the exon 1 was found for the β 2 receptor gene (B 2 R) BDKRB2, located in the chromosome 14 q32.1-q32.2, in which the absence (-9) and not the presence (+9) of a segment of 9 base pairs is associated with the high transcriptional activity of the gene and consequently, high response of the receptor to the agonist (3) .…”

“…Williams et al (43) while believing that part of ACE effects in the muscular contractile function may be mediated by bradykinin, studied in two distinct populations (115 healthy individuals and 81 British Olympic athletes) the muscular contractile efficiency for the different genotypes of the BDKRB2 gene, verified by the energy used per the 'efficiency delta' power unit (% of alteration in the work performed per minute/% of alteration in the energy spent per minute) and evaluated in cycle ergometer. For the 115 healthy individuals, the efficiency delta showed association with the +9/ +9, +9/-9 and -9/-9 genotypes (23.84 ± 2.41 vs. 24.25 ± 2.81 vs. 26.05 ± 2.26% respectively; p = 0.002).…”