title: G16R single nucleotide polymorphism but not haplotypes of the β(2)-adrenergic receptor gene alters cardiac output in humans.
abstract: Variation in genes encoding the β(2)-adrenergic receptor (ADRB2) and angiotensin-converting enzyme (ACE) may influence Q (cardiac output). The 46G>A (G16R) SNP (single nucleotide polymorphism) has been associated with β(2)-mediated vasodilation, but the effect of ADRB2 haplotypes on Q 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 Q. In carriers of the Arg(16) allele, Q(rest) (resting Q) 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 Q was by 4.7 (95% CI, 4.3-5.2) l/min per litre increase in pulmonary Vo(2) (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 Q 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 Q both at rest and during exercise, overriding the effects of haplotypes.
authors: Department of Anaesthesia, Rigshospitalet, University of Copenhagen, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark.
authors: Kim Z
authors: KZ
authors: Rokamp
authors: Jonatan M
authors: JM
authors: Staalsoe
authors: Martin
authors: M
authors: Gartmann
authors: Anna
authors: A
authors: Sletgaard
authors: Nicolai B
authors: NB
authors: Nordsborg
authors: Niels H
authors: NH
authors: Secher
authors: Henning B
authors: HB
authors: Nielsen
authors: Niels V
authors: NV
authors: Olsen
mesh_terms: D002302:Cardiac Output / Q000235:genetics*; D005080:Exercise Test; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D054643:INDEL Mutation; D020641:Polymorphism, Single Nucleotide; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
chemical_list: C553443:ADRB2 protein, human; D018343:Receptors, Adrenergic, beta-2