Effect of 393T>C polymorphism of GNAS1 gene on dobutamine response in Chinese healthy subjects.
The purpose of this study was to characterize the functional consequences of the 393T>C polymorphism of the GNAS1 gene in vivo. PCR-RFLP assays were used to identify GNAS1 and beta 1-adrenoceptor genotypes. The heart rate (HR), blood pressure, left ventricular fractional shortening (LVFS), and left ventricular ejection fraction (LVEF) were determined in different genotypes through a modified dobutamine stress echocardiography protocol. Our results showed that individuals with homozygous or heterozygous C393 had an increased cardiovascular agonistic response to dobutamine, and the increases from baseline in LVFS at the 3 dosage levels of dobutamine were 19.3% +/- 1.0% versus 32.0% +/- 2.9%, 36.7% +/- 3.1% versus 41.3% +/- 4.1%, and 51.7% +/- 3.3% versus 58.7% +/- 2.6% in T393 homozygotes and C393 homozygotes or heterozygotes, respectively (P = .026). Significant differences were also found between these 2 groups with the increases from baseline in LVEF (P = .007) and SBP (P = .048). In addition, there were significant differences in the increases from atopine in LVFS (P = .011), LVEF (P = .004), and SBP (P = .046) between the T393 homozygotes and C393 homozygotes or heterozygotes. The change of LVEF in C393 homozygous was higher than that in T393 homozygous at the dose of 40 microg/kg/min (28.9% +/- 4.0% vs 36.4% +/- 2.1%; 95% CI, 18.8%-38.9%; P = .046). These data suggested that the 393T>C polymorphism of GNAS1 was functionally relevant in vivo.
Mao
Yan-Mei
YM
Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan 410078, People's Republic of China.
Liu
Zhao-Qian
ZQ
Chen
Bi-Lian
BL
Guo
Dong
D
Han
Chun-Ting
CT
Yang
Li-Jun
LJ
Wang
Sai-Ying
SY
Fan
Lan
L
Zhou
Hong-Hao
HH
D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002681:China; D002864:Chromogranins; D004280:Dobutamine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D025401:Echocardiography, Stress; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D005838:Genotype; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics; D016277:Ventricular Function, Left / Q000187:drug effects; D055815:Young Adult
D000318:Adrenergic beta-Agonists; D002864:Chromogranins; D018342:Receptors, Adrenergic, beta-1; D004280:Dobutamine; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs