A comprehensive systematic review of studies on the potential of A49T and V89L polymorphism in SRD5AR2 as high susceptibility gene association with benign prostate hyperplasia and prostate cancer

Introduction and objectives: Being the most common disease in aged men, the etiology of Benign Prostatic Hyperplasia (BPH) is not fully defined. Recent studies have reported that the association between Benign Prostate Hyperplasia and metabolic genes is still inconsistent. A gene connected with BPH is SRD5AR2, whose polymorphisms, A49T and V89L, have distinct enzyme activity. This systematic review examines SRD5AR2 polymorphisms within two alleles (A49T and V89L), assessing their roles as prognostic indicators of malignancy, and response to medication. Materials and methods: We conducted a search on six different databases, including PubMed, Scopus, Wiley, ProQuest, Cochrane Central, and Science Direct using as string of keywords (BPH) AND [(rs523349) OR (V89L)] AND [(rs9282858) OR (A49T)]. We finally selected seven articles to be extracted. Quality appraisal of clinical trials was evaluated using the Joanna Briggs Institute Approach for systematic reviews. Results: We sorted nine clinical studies from various countries examining SRDA52 polymorphism and its association of BPH and prostate cancer. About V89L we found that the "LL" genotype, indicating reduced 5 alpha-reductase activity, is linked to a lower BPH risk, while the "VV" genotype may slightly increase BPH risk. About A49T, compared to "AA" genotype, "AT" tends to be associated to higher risk in developing prostate cancer. A49T polymorphism does not show any effect on medical treatment while V89L showed a protective effect on the clinical progression of BPH when treated with 5a-reductase inhibitors, aadrenergic receptor antagonists, and alpha blockers. Conclusions: SRD5A2 polymorphisms could be a good indicator for prognostic malignancy and a potential tool for personalized medicine of BPH. The findings strongly support the recommendation for further study about SRD5AR2 to enhance its use for screening and prevention and to optimize the medical treatment of Benign Prostatic Hyperplasia.