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Updated: May 13, 2025
Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
Published on: November 2, 2013
Analysis of Gene Polymorphisms in Benign Prostate Hyperplasia Patients Receiving Combination Therapy of Alpha Blocker
Besut Daryanto1, Taufiq Nur Budaya1, Widodo2
1Department of Urology, Faculty of Medicine, Universitas Brawijaya/Saiful Anwar General Hospital.
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.
Insights
A specific genetic marker, SNP rs61767072 in the SRD5A2 gene, strongly correlates with resistance to Benign Prostatic Hyperplasia (BPH) treatments. This finding supports the use of pharmacogenomics for personalized BPH therapy.
Area of Science:
- Genomics
- Personalized Medicine
- Urology
Background:
- 25-30% of Benign Prostatic Hyperplasia (BPH) patients do not respond to 5-Alpha Reductase Inhibitors (5-ARI).
- 7% of BPH patients experience disease progression despite 5-ARI treatment.
- Personalized medicine uses human genomics to tailor treatments and predict drug resistance.
Purpose of the Study:
- To identify genetic factors influencing BPH treatment outcomes.
- To advance personalized medicine for BPH.
- To improve therapeutic efficacy in BPH management.
Main Methods:
- Cohort study of BPH patients (responsive and resistant to treatment).
- DNA extraction and next-generation sequencing (NGS) post-prostate resection.
- Bioinformatic analysis of whole-genome sequencing (WGS) data against the Human GRCh38 reference genome.
Main Results:
- Identified two genetic variants associated with BPH: SNP rs1799983 (NOS3 gene) and SNP rs61767072 (SRD5A2 gene).
- All treatment-resistant BPH samples showed mutations in SNP rs61767072 (SRD5A2 gene deletion at base A).
- SNP rs61767072 strongly correlated with resistance to BPH combination therapy; NOS3 gene mutations showed no significant correlation.
Conclusions:
- Genetic variations significantly impact personalized medical care.
- SNP rs61767072 may serve as a basis for developing personalized BPH therapies.
- Pharmacogenomic approaches are essential for improving urological treatment outcomes.
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