Article - Association between vitamin D receptor gene polymorphisms and genetic susceptibility to benign prostatic hyperplasia: A systematic review and meta-analysis.

Expert Review

Reviewer: Chloe Steele

1st Feb 2026

Conflict of interest

None

Take home message

Genetic polymorphisms in the VDR gene may be associated with the risk for BPH. However, genetic testing may not be warranted at this stage. Dietary and lifestyle changes should form the basis of BPH management whilst ensuring adequate vitamin D status, especially in men with comorbidities.

Evidence category

A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)

Summary review

Introduction –

The identification of genetic polymorphisms in benign prostatic hyperplasia (BPH) has led to a change in its diagnosis and management.

In particular the vitamin D receptor (VDR) gene has been identified as a potential target due to the role of vitamin D in the transcriptional downregulation of genes involved in its development and the relationship between VDR polymorphisms and the prevalence of BPH in many populations.

Previous meta-analyses failed to come to definitive conclusions on the relationship between VDR and BPH so this systematic review and meta-analysis of 10 papers on VDR polymorphisms and BPH aimed to update previous research.

Methods –

• 10 papers on VDR polymorphisms and the risk for BPH were included.

•1539 individuals with BPH and 1915 controls.

• Papers were case-control or cohort studies.

• VDR gene polymorphisms assessed were Apa-1, Bsm-I, Taq-1, and Fok-1.

• Studies were written in Chinese and English and achieved more than 5 points on the Newcastle Ottawa Scale.

• Publication bias was assessed using the Begg and Egger test.

Results –

• In the overall population, an association between the Taq-1 polymorphism and BPH risk was found (P<0.001).

• Individuals with the dominant W allele had an increased risk of BPH compared to those with the ww allele or no W allele (WW vs ww: OR = 2.194, 95% CI = 1.384–3.196, P <0.001; WW vs Ww: OR = 1.562, 95% CI = 1.207–2.021, P = 0.001; WW vs Ww/ww: OR = 1.673, 95% CI = 1.312–2.133, P = 0; W vs w allele: OR = 1.443, 95% CI = 1.205–1.730, P <0.001).

• Those with the recessive allele showed a lower risk for BPH (WW/Ww vs ww: OR = 0.558, 95% CI = 0.392–0.795, P = 0.001)

• Amongst Caucasian and Asian participants an association between the recessive (Caucasian: 95% CI = 0.100–0.943, P = 0.039; Asian: 95% CI = 1.242–3.283, P = 0.039) and over-dominant (Caucasian: 95% CI = 1.553–3.100, P <0.001; Asian: 95% CI = 0.281–0.680, P <0.001) Bsm-1 variants was seen.

Conclusion –

Taq-1 polymorphisms may be a genetic biomarker that can be used to predict the development of BPH.

Clinical practice applications

• Whilst the Taq-1 genetic polymorphism is an indicator of risk, it is not a predictor of development.

• The effect sizes were relatively small and given the lack of availability and cost of genetic testing it does not justify routine genetic testing at this stage.

• There may be some benefit of vitamin D testing to ensure there are no deficiencies which may exacerbate the effects of the VDR polymorphism.

• Management of BPH should still include dietary and lifestyle changes with a particular focus on inflammation.

Considerations for future research

• There are several VDR polymorphisms, and all could be assessed for their association with BPH risk.

• Genetic effects may only appear under certain environmental conditions and the effects of sun exposure could be investigated.

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Abstract

BACKGROUND

Benign prostatic hyperplasia (BPH) is one of the global public health challenges due to the complexity of its mechanisms of occurrence. Many studies have suggested that vitamin D receptor gene polymorphisms are associated with BPH susceptibility. Still, their conflicting findings need to be analyzed in aggregate to gain a better understanding.

METHODS

We identified 10 trials involving 1539 BPH cases and 1915 controls through a systematic search of Embase using, data obtained from the Web of Science, PubMed, and China Knowledge Network databases as of December 31, 2021. A meta-analysis was performed to investigate the association between 4 constant polymorphisms of this associated vitamin D receptor gene (Fok-1, Bsm-1, Taq-1, and Apa-1) and BPH risk.

RESULTS

In the overall population analysis, a significant positive association with BPH risk was found only in the Taq-1 variant (P < .001). Of these, the pure-hybrid model (95% confidence interval [CI] = 1.384-3.196), the heterozygous model (95% CI = 1.207-2.021), the dominant model (95% CI = 1.312-2.133) and the allelic inheritance model (95% CI = 1.205-1.730) showed low heterogeneity. In subtype analyses, Bsm-1 variants showed a significant association with BPH risk for both the recessive (95% CI = 0.100-0.943, P = .039) and over-dominant (95% CI = 1.553-3.100, P = 0) models in the Caucasian population, and for the recessive (95% CI = 1.242-3.283, P = .039) and over-dominant (95% CI = 0.281-0.680, P = 0) models in the Asian population. In addition, a high degree of heterogeneity was found in the subgroup analysis of the association between Fok-1 variants and BPH risk.

CONCLUSION

Overall, there is an association between vitamin D receptor polymorphisms and BPH risk. Identification of BPH susceptibility by vitamin D receptor gene polymorphisms has potential.