BPH Patients’ Response to Drug Therapy May Have a Genetic Determinant

BPH Patients’ Response to Drug Therapy May Have a Genetic Determinant

Natural variations, called polymorphisms, in a nitric oxide coding gene may affect a benign prostatic hyperplasia (BPH) patient’s response to drug therapy for lower urinary tract symptoms (LUTS), according to a study, “The association of eNOS G894T gene polymorphisms with responsiveness to α1-blocker in men with BPH/LUTS,” published in the BJU International journal.

In elderly males, benign prostatic hyperplasia is the most common cause of lower urinary tract symptoms that usually include weak urinary stream, feeling of incomplete bladder emptying, urinary hesitancy, frequent urination, and urge incontinence.

Recently, nitric oxide (NO) was recognized as an important neurotransmitter and cell-signaling molecule capable of regulating a broad range of functions in the lower urinary tract. As such, alterations in genes coding for key enzymes of NO production, such as endothelial NOS (eNOS), could impact how patients respond to treatments for BPH/LUTS, such as α1-blockers. These drugs, also called alpha-adrenergic blocking agents, block α1-adrenergic receptors in arteries, smooth muscles, and central nervous system tissues.

Researchers performed a prospective study and investigated how the association of eNOS G894T gene polymorphism impacts BPH/LUTS patients’ response to an α1-blocker. They recruited 136 patients with BPH/LUTS from a medical university in Taiwan. Patients, who had received no prior treatment for their symptoms, were treated for 12 weeks with doxazosin-GITS (administered orally). Treatment efficacy was assessed by changes relative to baseline scores in the International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax), and post-void residual urine volume (PVR). In parallel, researchers determined patients carrying the eNOS G894T polymorphisms by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

The team observed that patients exhibited a significant improvement over the 12-week treatment period in total IPSS, Qmax and quality of life. Moreover, they found that carrying the eNOS G894T polymorphism had a significantly negative effect on patients’ response to an α1-blocker in BPH/LUTS treatment.

These results suggest that eNOS G894T gene polymorphisms are potential genetic alterations that affect a drug’s efficacy in men with BPH/LUTS. Additional large-scale genetic epidemiological studies are, however, required to confirm and further investigate the causes for genetic susceptibility to drug responsiveness in BPH/LUTS.

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Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.

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