Genetic risk factors for erectile dysfunction and genetic determinants of drug response--on the way to improve drug safety?
Association studies give hint for the fact that the risk to develop cardiovascular disorders such as hypertension or coronary heart disease is influenced by the genotype in single nucleotide polymorphisms (SNPs). Considering the close relationship in the pathophysiology of these diseases and erectile dysfunction (ED), the analysis of the association of genotypes in SNPs and ED stands to reason. In an analysis of ED patients and their genotypes in the GNB3 C825T, the ACE I/D and the NOS3 G894T polymorphisms, there was no evidence for influence of the genotypes on the susceptibility to develop ED. At the same time, a significant variation in drug response to sildenafil dependent on the genotypes in the GNB3 C825T and ACE I/D polymorphisms was demonstrated. In the group of GNB3 825C allele carriers, only 50% of patients showed a positive response, while > 90% of the patients genotype TT responded adequately. In parallel, only 50% of ACE D allele carriers showed a positive response to sildenafil in contrast to men genotype II in the ACE I/D polymorphism, who had a response rate of 75%. Considering cardiovascular side effects under sildenafil treatment, it would be interesting to determine if genetic factors have an impact on the side effect profile of this drug.
Eisenhardt
Andreas
A
Institute of Pharmacology, University Hospital Essen, Germany. Andreas.Eisenhardt@uni-essen.de
Siffert
Winfried
W
D000803:Angiotensin I / Q000235:genetics; D000818:Animals; D007172:Erectile Dysfunction / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000803:Angiotensin I; D000068677:Sildenafil Citrate; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III