G16R single nucleotide polymorphism but not haplotypes of the ß2-adrenergic receptor gene alters cardiac output in humans

TY - JOUR

T1 - G16R single nucleotide polymorphism but not haplotypes of the ß2-adrenergic receptor gene alters cardiac output in humans

AU - Rokamp, Kim Z

AU - Staalsø, Jonatan M

AU - Gartmann, Martin

AU - Sletgaard, Anna

AU - Nordsborg, Nikolai Baastrup

AU - Secher, Niels H

AU - Nielsen, Henning B

AU - Olsen, Niels V

N1 - CURIS 2013 NEXS 102

PY - 2013/8

Y1 - 2013/8

N2 - Variation in genes encoding the β2-adrenergic receptor (ADRB2) and angiotensin-converting enzyme (ACE) may influence Q̇ (cardiac output). The 46G>A (G16R) SNP (single nucleotide polymorphism) has been associated with β2-mediated vasodilation, but the effect of ADRB2 haplotypes on Q̇ has not been studied. Five SNPs within ADRB2 (46G>A, 79C>G, 491C>T, 523C>A and 1053G>C by a pairwise tagging principle) and the I/D (insertion/ deletion) polymorphism in ACE were genotyped in 143 subjects. Cardiovascular variables were evaluated by the Model flow method at rest and during incremental cycling exercise. Only the G16R polymorphism was associated with Q̇ . In carriers of the Arg16 allele, Q̇rest (resting Q̇ ) was 0.4 [95% CI (confidence interval), 0.0-0.7] l/min lower than in G16G homozygotes (P=0.048). During exercise, the increase in Q̇ was by 4.7 (95% CI, 4.3-5.2) l/min per litre increase in pulmonary V̇o2 (oxygen uptake) in G16G subjects, but the increase was 0.5 (0.0-0.9) l/min lower in Arg16 carriers (P=0.035). A similar effect size was observed for the Arg16 haplotypes ACCCG and ACCCC. No interaction was found between ADRB2 and ACE polymorphisms. During exercise, the increase in Q̇ was 0.5 (CI, 0.0 -1.0) l/min greater in ACE I/I carriers compared with I/D and D/D subjects (P=0.054). In conclusion, the ADRB2 Arg16 allele in humans is associated with a lower Q̇ both at rest and during exercise, overriding the effects of haplotypes.

AB - Variation in genes encoding the β2-adrenergic receptor (ADRB2) and angiotensin-converting enzyme (ACE) may influence Q̇ (cardiac output). The 46G>A (G16R) SNP (single nucleotide polymorphism) has been associated with β2-mediated vasodilation, but the effect of ADRB2 haplotypes on Q̇ has not been studied. Five SNPs within ADRB2 (46G>A, 79C>G, 491C>T, 523C>A and 1053G>C by a pairwise tagging principle) and the I/D (insertion/ deletion) polymorphism in ACE were genotyped in 143 subjects. Cardiovascular variables were evaluated by the Model flow method at rest and during incremental cycling exercise. Only the G16R polymorphism was associated with Q̇ . In carriers of the Arg16 allele, Q̇rest (resting Q̇ ) was 0.4 [95% CI (confidence interval), 0.0-0.7] l/min lower than in G16G homozygotes (P=0.048). During exercise, the increase in Q̇ was by 4.7 (95% CI, 4.3-5.2) l/min per litre increase in pulmonary V̇o2 (oxygen uptake) in G16G subjects, but the increase was 0.5 (0.0-0.9) l/min lower in Arg16 carriers (P=0.035). A similar effect size was observed for the Arg16 haplotypes ACCCG and ACCCC. No interaction was found between ADRB2 and ACE polymorphisms. During exercise, the increase in Q̇ was 0.5 (CI, 0.0 -1.0) l/min greater in ACE I/I carriers compared with I/D and D/D subjects (P=0.054). In conclusion, the ADRB2 Arg16 allele in humans is associated with a lower Q̇ both at rest and during exercise, overriding the effects of haplotypes.

U2 - 10.1042/cs20120555

DO - 10.1042/cs20120555

M3 - Journal article

C2 - 23438238

SN - 0143-5221

VL - 125

SP - 191

EP - 198

JO - Clinical Science

JF - Clinical Science

IS - 4

ER -