Genetic variants in 5p13.2 and 7q21.1 are associated with treatment for benign prostatic hyperplasia with the α-adrenergic receptor antagonist

Abstract

Background: The etiology of benign prostatic hyperplasia (BPH) has not been well established. The preferred medical treatment for many men with symptomatic benign prostatic hyperplasia is either an α-adrenergic receptor antagonist (α-blocker), or a 5α-reductase inhibitor. Single nucleotide polymorphism (SNP) is a powerful tool for successful implementation of individualized treatment.

Methods: Eighteen SNPs associated with drug efficacy in a Chinese population were genotyped in 790 BPH cases (330 aggressive and 460 non-aggressive BPH cases) and 1008 controls. All BPH patients were treated with α-adrenergic blockers for at least 9 months. We tested the associations between tagging single nucleotide polymorphism and BPH risk/aggressiveness, clinical characteristics at baseline, including the International Prostate Symptom Score (IPSS) and total prostate volume, and changes in clinical characteristics after treatment.

Results: There were nine SNPs associated with BPH risk, clinical progression and therapeutic effect. (1) There were nine tSNPs been chosen in CYP3A4, CYP3A5 and RANBP3L genes. (2) The SNP, rs16902947 in RANBP3L at 5p13.2 (p = .01), was significantly associated with BPH. (3) We found two SNPs, rs16902947 in RANBP3L at 5p13.2 (p = .0388) and rs4646437 in CYP3A4 at 7q21.1 (p = .0325), associated with drug effect. (4) Allele “G” for rs16902947 was found to be risk alleles for BPH risk (OR= 2.357, 95%CI 1.01–1.48). The “A” allele of rs4646437 was associated with lower IPSS at baseline (β= −0.4232, p= .03255).

Conclusions: rs16902947, rs16902947 and rs4646437 single nucleotide polymorphisms are significantly associated with the clinical characteristics of benign prostatic hyperplasia and the efficacy of benign prostatic hyperplasia treatment.

Keywords:

• Benign prostatic hyperplasia
• α-adrenergic receptor antagonists
• aggressive
• single nucleotide polymorphism (SNP)

Disclosure statement

There is no conflict of interest in the body of this manuscript.

Ethical standards and informed consent

The research ethics was approved by Xinhua Hospital.

All the patients gave written informed consent before participation in this study.

Additional information

Funding

This research was partly supported by the National Natural Science Foundation of China (No. 81570684) and Shanghai Municipal Science and Technology Commission (No. 14430720800 and No. 15ZR1427600).