The association of endothelial nitric oxide synthase ( eNOS) G894T gene polymorphism with responsiveness to a selective α1-blocker in men with benign prostatic hyperplasia related lower urinary tract symptoms.

Objective To prospectively investigate the association of endothelial nitric oxide synthase ( eNOS) G894T gene polymorphism with responsiveness to a selective α₁-blocker in men with benign prostatic hyperplasia related lower urinary tract symptoms ( BPH/ LUTS), as nitric oxide has recently gained increasing recognition as an important neurotransmitter of functions in the lower urinary tract. Patients and Methods In all, 136 men with BPH/ LUTS were recruited from urology outpatient clinics in a university hospital. Oral therapy with doxazosin gastrointestinal therapeutic system ( GITS) 4 mg once-daily was given for 12 weeks. The drug efficacy was assessed by the changes from baseline in the total International Prostate Symptom Score ( IPSS), maximum urinary flow rate ( Q_max) and post-void residual urine volume ( PVR) at 12 weeks of treatment. The 'responders' to doxazosin GITS were defined as those who had a total IPSS decrease of >4 points from baseline. eNOS G894T polymorphism was determined using the polymerase chain reaction-restriction fragment length polymorphism method. Results Patients had statistically significant improvements in total IPSS, quality of life score, and Q_max ( P < 0.01) after a 12-week period of treatment. Using multiple logistic regression analysis adjusted for age and IPSS, our results showed that being a eNOS 894T allele carrier was an independent risk factor for being a drug non-responder ( P = 0.03, odds ratio 4.19). Moreover, a decreased responder rate ( P = 0.01), as well as the lower improvements in IPSS ( P = 0.02) and Q_max ( P = 0.03) were significantly associated with increment in the T allele number. Conclusions The presence of the eNOS 894T allele had a significantly negative impact on responsiveness to a selective α₁-blocker in BPH/ LUTS treatment, suggesting that eNOS G894T gene polymorphism may be a genetic susceptibility factor for α₁-blocker efficacy in men with BPH/LUTS. [ABSTRACT FROM AUTHOR]