Systematic review and meta-analysis of candidate gene association studies of benign prostate hyperplasia.

Lin Lin, Pugui Li, Xin Liu, Xiuyuan Xie, Liping Liu, Anjani Kumar Singh, Himanshu Narayan Singh

Journal: Systematic reviews 2022;11(1):60

PMID: 35382870

Plain Language Summary

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Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate which can cause urinary dysfunction and may affect the quality of life of patients. Polymorphism in several genes has been linked to the high susceptibility of BPH. The aim of this study was to analyse genetic variations in important genes towards the susceptibility of BPH. This study is a systematic review and meta-analysis of twenty-three case-control studies (11 for CYP17 [gene], 10 for VDR - vitamin D receptor [a member of the steroid/ thyroid hormone receptor family] and 4 for ACE - angiotensin-converting enzyme [component of the renin–angiotensin system] polymorphisms). The sample size in each study ranged from 20 to 588 participants. Results show that genetic polymorphism in the ACE gene was significantly associated with the risk of BPH when compared with control subjects. Whereas there was a negative association for the polymorphism located in VDR and CYP17 genes with the risk of BPH. Authors conclude that larger studies with prospective data and larger sample sizes are required.

Abstract

BACKGROUND

Benign prostate hyperplasia (BPH) is the most common urological problem in elderly males. Recent studies have reported polymorphism in various metabolic genes in BPH. However, their association with the susceptibility of BPH is still inconsistent. Here, we systematically reviewed and performed a meta-analysis of CYP17, VDR, and ACE genes to determine their precise association with the risk of BPH.

METHODS

A comprehensive literature search for published studies on candidate gene associations involving vitamin D receptor (VDR), angiotensin-converting enzyme (ACE), and CYP17 genes with the risk of BPH was done up to April 2020 in PubMed, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases. Fixed/random effects models were used to estimate the odd's ratio (OR) and 95% confidence intervals (CIs). Begg's funnel plot was used to assess the potential for publication bias.

RESULTS

We found a total of 23 studies containing 3461 cases and 3833 controls for these gene polymorphisms. A significant association of ACE gene polymorphism was observed under the recessive (II vs. ID + DD) model for BPH susceptibility compared to control subjects (overall OR = 1.67, 95% CI = 1.03-2.73). Similar trends were observed for ACE gene polymorphism in Caucasian (OR = 6.18, 95% CI = 1.38-27.68) and Asian (OR = 1.42, 95% CI = 0.99-2.03) populations under study. No significant association was observed in VDR and CYP17 gene polymorphisms in any dominant or recessive models.

CONCLUSION

Significant OR demonstrated the implication of ACE gene polymorphism in the proliferation of prostate tissue, which in turn is associated with BPH susceptibility. However, prospective studies at large scale and sample size are needed to confirm the current findings.

© 2022. The Author(s).

Address: Department of Urology, Hospital of Traditional Chinese and Western Medicine of Taizhou, Taizhou, 317502, Zhejiang, China.; Department of Urology, Tangdu Hospital,Air Force Military Medical University, Xi'an, Shaanxi, 710032, China.; Department of Critical Care Medicine, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi Municipality, 830000, Xinjiang, China.; Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing City, 210029, Jiangsu, China.; Department of Outpatient, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou City, 510260, Guangdong, China. [email protected].; Department of Physics, Atma Ram Sanatan Dharma College, University of Delhi, New Delhi, India.; TAGC, Aix Marseille University, Marseille, France.
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