Analysis of AR, PSA (KLK) and ER-β genetic variants and Benign Prostate Hyperplasia (BPH) pathogenesis in Indian population

Abstract

Benign Prostate Hyperplasia (BPH) pathogenesis exhibitsinter-individual variation in the genome as polymorphisms in the steroid hormone genes AR, PSA (KLK) and ER-β profound effects in altering BPH disease progression rate. Single nucleotide polymorphisms (SNPs) designated 1754 A/G exon-1 in AR, Promotor-158 A/G in PSA(KLK) and 1730 A/G 3’UTR in Exon-8 in ER-β have been associated with BPH pathogenesis. In the current study, AR-1754 A/G exon-1, PSA-ARE1 Promotor-158 A/G and 1730 A/G 3’UTR in Exon-8 in ER-β were analysed in Indian population.The polymorphisms in BPH patients and healthy individuals were evaluated by PCR, RFLP–PCR and genotype–phenotype correlation. In the study AR and ER-β SNPs demonstrated significant association [55.7% (OR 3.0 (95% CI 1.67–5.46) (p 0.0002)] and [52.6 % (OR 6.5, 95% CI 3.27–12.74) (p 0.0001)] with BPH pathogenesis in patients as compared to control. With both the polymorphisms indicating a trend towards an association of the G allele with an increased risk of BPH pathogenesis. The A/G genotype frequency of PSA was 54 % in patients and was not associated with BPH pathogenesis. Further genotype–phenotype correlation study has provided evidence that gene–gene interactions play an important role in the etiology of BPH. Although susceptibility to pathogenesis cannot be dependent on a single or small number of genetic variants, it is noteworthy that AR, PSA and ER-β variants have been correlated globally with BPH pathogenesis. Hence, the higher frequency of AR and ER-β variants in the Indian population may be critical in BPH pathogenesis.