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.
[Acta Inform Med 2025; 33(1.000): 54-57]

BPH, Genomic, Personalized Medicine, Whole Gene Sequencing