title: Polymorphism of the G protein β3 subunit gene influences the efficacy of sildenafil in patients with pulmonary hypertension.
abstract: OBJECTIVE
  The C825T polymorphism in the G protein β3 subunit gene (GNB3) influences the efficacy of sildenafil in patients with erectile dysfunction. The effects of this polymorphism on the therapeutic response to sildenafil in patients with pulmonary hypertension remains unknown. To investigate whether the GNB3C825T polymorphism is associated with the clinical efficacy of sildenafil in patients with pulmonary hypertension.
  
  
  METHODS
  Fifty-nine patients (age: 55.6 ± 13.3 [SD] yrs., mean pulmonary arterial pressure (Ppa): 52 ± 11 mmHg) with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension were treated with sildenafil. The pre- and post-treatment parameters, including pulmonary hemodynamics measured using right heart catheterization, the systolic pulmonary arterial pressure estimated on Doppler echocardiography (sPA), the six-minute walk distance (6MWD) and freedom from clinical worsening, were compared between the patients with the TT and CT/CC genotypes.
  
  
  RESULTS
  The pretreatment parameters were not significantly different between the two groups, with the exception of a lower mean Ppa in the TT group. The post-treatment World Health Organization (WHO) class was significantly better (p=0.03) and the 6MWD values trended toward improvement in the TT genotype patients compared with that observed in the CC/CT genotype patients (p=0.05). The time to clinical worsening was significantly longer in the TT genotype patients than in the CC/CT genotype patients (3-year freedom from clinical worsening: 83.1% vs. 46.0%, p=0.02), while the TT genotype was found to be a significant predictor of freedom from clinical worsening, even after adjusting for the baseline mean Ppa.
  
  
  CONCLUSIONS
  The GNB3 C825T polymorphism influences the efficacy of sildenafil in patients with pulmonary hypertension.
authors: Department of Respirology, Graduate School of Medicine, Chiba University, Japan.
authors: Ayumi
authors: A
authors: Sekine
authors: Nobuhiro
authors: N
authors: Tanabe
authors: Toshihiko
authors: T
authors: Sugiura
authors: Ayako
authors: A
authors: Shigeta
authors: Takayuki
authors: T
authors: Jujo
authors: Rintaro
authors: R
authors: Nishimura
authors: Seiichiro
authors: S
authors: Sakao
authors: Yasunori
authors: Y
authors: Kasahara
authors: Koichiro
authors: K
authors: Tatsumi
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011687:Purines / Q000627:therapeutic use; D012189:Retrospective Studies; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use*; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects
chemical_list: C454420:G-protein beta3 subunit; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D020962:Heterotrimeric GTP-Binding Proteins