Association of CCL2, CCR2 and CCL5 genetic polymorphisms with the development and progression of benign prostatic hyperplasia

Abstract

Benign prostatic hyperplasia (BPH) is a common chronic disease in older males. The pathogenesis of BPH remains elusive but may be associated with chronic inflammation. Chemokines and chemokine receptors have been implicated as critical mediators in the immune response and inflammatory processes. In the present study, the aim was to evaluate the association of three polymorphisms in chemokine genes, namely C-C motif chemokine ligand (CCL)2 rs1024611, CC chemokine receptor 2 (CCR2) rs1799864 and CCL5 rs2107538, with BPH risk. These polymorphisms were genotyped in 109 patients with BPH and 160 control subjects, using the polymerase chain reaction and multiple ligase detection reaction method. The CCL5 rs2107538 polymorphism was identified to be associated with a significantly lower risk of BPH [A/G vs. G/G: Odds ratio (OR)=0.37, 95% confidence interval (CI)=0.17‑0.78; A/A+A/G vs. G/G: OR=0.39, 95% CI=0.19‑0.79; A vs. G: OR=0.58, 95% CI=0.35-0.96). However, this polymorphism was also associated with the development of larger prostate volumes in patients with BPH (A/G vs. G/G: OR=3.02, 95% CI=1.28‑7.11; AA + AG vs. GG: OR=2.83, 95% CI=1.28‑6.26; A vs. G: OR=1.94, 95% CI=1.08-3.49). The CCR2 rs1799864 polymorphism was associated with lower International Prostate Symptom Score values (A/A+A/G vs. G/G: OR=0.39, 95% CI=0.17‑0.91; A vs. G: OR=0.43, 95% CI=0.20‑0.90) and low Qmax (A/G vs. G/G: OR=0.38, 95% CI=0.16‑0.92; AA+AG vs. GG: OR=0.39, 95% CI=0.17-0.91) in the patients. No association was observed between the CCL2 rs1024611 polymorphism and BPH. These results suggest that the CCR2 and CCL5 genes may contribute to the occurrence and progression of BPH.