Sildenafil response is influenced by the G protein beta 3 subunit GNB3 C825T polymorphism: a pilot study.
OBJECTIVE
Sildenafil is the oral phosphodiesterase-5 inhibitor that revolutionized treatment for erectile dysfunction. We investigated a potential association of the G protein beta 3 subunit (GNB3) C825T polymorphism, a determinant of intracellular signal transduction, with the drug response to sildenafil in patients with erectile dysfunction.


METHODS
In 113 men with erectile dysfunction and 111 healthy male controls genotype status of the GNB3 C825T polymorphism was determined by polymerase chain reaction and restriction analysis. Patients with erectile dysfunction received sildenafil at a dose of 25 to 100 mg. according to the individual erectile response. Drug response was measured by interviewing the patient according to the erection scale of 0 to 5.


RESULTS
The GNB3 genotype distribution of patients with erectile dysfunction exactly matched that of healthy controls. Analysis of the response to sildenafil revealed a significant association of C825T allele status with the erectile response to sildenafil. In the group with TT genotype we observed a 90.9% response but only a 50.9% and 48.9% response in patients with the CC and TC genotype, respectively. The odds ratio for a positive erectile response was 10.0 (95% CI 1.2 to 81.1) for patients with the TT versus the TC/CC genotype (p = 0.01).


CONCLUSIONS
The response to sildenafil is significantly associated with GNB3 C825T genotype status in patients with erectile dysfunction.
Sperling
Herbert
H
Department of Urology, University Hospital Essen, Germany.
Eisenhardt
Andreas
A
Virchow
Sebastian
S
Hauck
Ekkehard
E
Lenk
Severin
S
Porst
Hartmut
H
Stief
Christain
C
Wetterauer
Ulrich
U
Rubben
Herbert
H
Muller
Norbert
N
Siffert
Winfried
W
D000483:Alleles; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000235:genetics; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010410:Penile Erection / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010865:Pilot Projects; D010879:Piperazines / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D021122:Protein Subunits / Q000235:genetics*; D011687:Purines; D012189:Retrospective Studies; D015398:Signal Transduction / Q000235:genetics; D000068677:Sildenafil Citrate; D013450:Sulfones; D014665:Vasodilator Agents / Q000627:therapeutic use*
C454420:G-protein beta3 subunit; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D021122:Protein Subunits; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D020962:Heterotrimeric GTP-Binding Proteins