G16R single nucleotide polymorphism but not haplotypes of the ß2-adrenergic receptor gene alters cardiac output in humans
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G16R single nucleotide polymorphism but not haplotypes of the ß2-adrenergic receptor gene alters cardiac output in humans. / Rokamp, Kim Z; Staalsø, Jonatan M; Gartmann, Martin; Sletgaard, Anna; Nordsborg, Nikolai Baastrup; Secher, Niels H; Nielsen, Henning B; Olsen, Niels V.
I: Clinical Science, Bind 125, Nr. 4, 2013, s. 191-198.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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
Y1 - 2013
N2 - Variation in genes encoding the ß2-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 ß2-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 Arg16 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 V¿O2 (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.
AB - Variation in genes encoding the ß2-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 ß2-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 Arg16 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 V¿O2 (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.
U2 - 10.1042/CS20120555
DO - 10.1042/CS20120555
M3 - Journal article
C2 - 23438238
VL - 125
SP - 191
EP - 198
JO - Clinical Science
JF - Clinical Science
SN - 0143-5221
IS - 4
ER -
ID: 45708594