Abstract

Background: Out of 25-30% of individuals do not respond to 5-Alpha Reductase Inhibitors (5-ARI) as a primary treatment of Benign Prostatic Hyperplasia (BPH), 7% experience disease progression despite treatment. Personalized medicine, which leverages human genomics, offers an approach to tailor treatments based on individual genetic profiles, facilitating early detection of drug resistance and optimizing therapeutic strategies. Objective: The aim of the study was to advance personalized medicine in BPH by identifying genetic factors that influence treatment outcomes, thus improving therapeutic efficacy. Methods: This cohort study involved patients responsive and resistant to treatment of BPH. After prostate resection, DNA was extracted and subjected to protein sequencing. The quality of the DNA was assessed, and next-generation sequencing (NGS) was performed. The sequencing data analyzed using FastQC, Samtools, MuTect2, ANNOVAR, and VEP. Whole-genome sequencing (WGS) data were compared to the Human GRCh38 reference genome. Single nucleotide polymorphisms (SNPs) and their positions were visualized through Integrated Genomics Viewer (IGV). Statistical analyses were conducted using R software. Result: Two genetic variants associated with BPH, was a single nucleotide polymorphism (SNP) in the NOS3 gene at rs1799983 (T>A/G), and an SNP at rs61767072 in the SRD5A2 gene. All samples that exhibited resistance to combination drug therapy showed mutations in SNP rs61767072, specifically a deletion at base A in the SRD5A2 gene. Strong correlation reported between SNP rs61767072 and resistance to BPH combination therapy while mutations involving base A and base G in the NOS3 gene did not exhibit any significant correlation with resistance to BPH combination therapy. Conclusion: Variations in genetic makeup significantly affect personalized medical care. Identification of specific SNPs such as rs61767072 may be the basis for the development of more personalized therapies. This study provides evidence that pharmacogenomic approaches are needed in urology practice to improve treatment outcomes.

Key words: BPH, Genomic, Personalized Medicine, Whole Gene Sequencing.