1. 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
- Author
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Yung-Shun Juan, Chia-Chu Liu, Yung-Chin Lee, Chii-Jye Wang, Wen-Jeng Wu, Shu-Pin Huang, Chun-Nung Huang, and Bo-Ying Bao
- Subjects
Adult ,Male ,medicine.medical_specialty ,Nitric Oxide Synthase Type III ,Urology ,Urinary system ,030232 urology & nephrology ,Prostatic Hyperplasia ,urologic and male genital diseases ,03 medical and health sciences ,0302 clinical medicine ,Lower Urinary Tract Symptoms ,Enos ,Lower urinary tract symptoms ,Doxazosin ,medicine ,Outpatient clinic ,Humans ,Prospective Studies ,Aged ,Aged, 80 and over ,Polymorphism, Genetic ,biology ,business.industry ,Odds ratio ,Middle Aged ,biology.organism_classification ,medicine.disease ,Treatment Outcome ,030220 oncology & carcinogenesis ,Adrenergic alpha-1 Receptor Antagonists ,International Prostate Symptom Score ,Gene polymorphism ,business ,medicine.drug - Abstract
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 (Qmax ) 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 Qmax (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 Qmax (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.
- Published
- 2016