Polymorphisms in the alpha1A-adrenoceptor gene do not modify the short- and long-term efficacy of alpha1-adrenoceptor antagonists in the treatment of benign prostatic hyperplasia.
OBJECTIVE To determine whether a common single nucleotide polymorphism (SNP) in the ADRA1A gene encoding the alpha(1A)-adrenoceptor modifies the short- and long-term efficacy of alpha(1)-adrenoceptor antagonists in the treatment of benign prostatic hyperplasia (BPH). PATIENTS AND METHODS For 254 patients with BPH and/or lower urinary tract symptoms who received alpha(1)-adrenergic antagonists for > or = 3 months, the ADRA1A genotype at position 1475 of the coding region was determined. The patients' short-term response to treatment was determined for four outcome measures, i.e. the International Prostate Symptom Score (IPSS), the IPSS quality-of-life score, peak urinary flow rate, and obstruction grade, stratified by genotype. Eventual BPH-related invasive therapy was used as the outcome for assessing the long-term response to treatment. Genetic variants at positions 834, 896, 898 and 1831 were too rare to be considered in the analysis. RESULTS There were no significant differences for the genotype strata in three of the four outcome measures. Patients with the CC genotype responded significantly better in quality-of-life perception than patients with the CT or TT genotype. There were also no significant differences in the risk of BPH-related invasive therapy among the three genotypes. CONCLUSIONS The 1475C-->T SNP in the ADRA1A gene does not modify the short- and long-term efficacy of alpha(1)-adrenoceptor antagonists for treating BPH. There was a small effect on perceived quality of life but this was not reflected in other variables that measured the treatment response more directly.
Department of Urology (G4-105.1), Academic Medical Centre, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. C.A.Mochtar@amc.uva.nl
Chaidir A
CA
Mochtar
Wijnand
W
Laan
Kjeld P
KP
Van Houwelingen
Barbara
B
Franke
Jean J M C H
JJ
De La Rosette
Jack A
JA
Schalken
Lambertus A L M
LA
Kiemeney
D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000368:Aged; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000235:genetics; D011788:Quality of Life; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics*; D012307:Risk Factors; D016896:Treatment Outcome
C547713:ADRA1A protein, human; D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1