Sildenafil response is influenced by the G protein beta 3 subunit GNB3 C825T polymorphism: a pilot study.

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Sperling H, Eisenhardt A, Virchow S, Hauck E, Lenk S, Porst H, Stief C, Wetterauer U, Rubben H, Muller N, Siffert W

Sildenafil response is influenced by the G protein beta 3 subunit GNB3 C825T polymorphism: a pilot study.

J Urol. 2003 Mar;169(3):1048-51.

PubMed ID

12576843 [ View in PubMed

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Abstract

PURPOSE: 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. MATERIALS AND 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.

DrugBank Data that Cites this Article

Pharmaco-genomics

Drug	Interacting Gene/Enzyme	Allele name	Genotypes	Defining change(s)	Type(s)	Description	Details
Sildenafil	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 Gene symbol: GNB3 UniProt: P16520	---	(T;T)	T allele, homozygote (rs5443)	Effect Directly Studied	Patients with this genotype have increased frequency of positive erectile response when using sildenafil to treat erectile dysfunction	Details