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.

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

“…The insertion/deletion polymorphism of the ACE gene is directly related to ACE plasma levels [ 50 ]. This variation has also previously been found to be associated with LUTS or surgery for LUTS in study populations of Mexico and India [ 43 , 45 ]. Thus, such reports prove the robustness of the current study.…”

“…Polymorphism in several genes has been linked to the high susceptibility of BPH. For example, SNPs in CYP17, CYP19, VDR, and SRD5A2 [ 34 ] and in chemokine genes CCR2 (rs1799864) and CCL5 (rs2107538) [ 45 ] genes have been reported in BPH. Individuals with metabolic syndrome (MetS) or its individual components—including central obesity, hyperinsulinemia, insulin resistance, and dyslipidemia, are more prone to develop BPH and LUTS [ 46 – 48 ].…”

Estrogen regulates the proliferation and inflammatory expression of primary stromal cell in benign prostatic hyperplasia

“…Yoo et al (14) reported that there is a strong association between IL10 and BPH in Korean population. Furthermore, other studies have illustrated that both chronic inflammation and immune dysregulation play significant roles in the progression of BPH (15,28,29). Finally, further studies are needed to explore molecular mechanisms and signal pathways activated by estrogen in the pathogenesis of BPH.…”

Inflammation and cancer interconnection; simply as we think

“…The interconnection between inflammation and cancer initiation is not a one-way street and there is also evidence that DNA damage can result in inflammation and thereby enhance tumorigenesis (Figure 4). One of the best examples is provided by the model of hepatocellular carcinoma induced by the carcinogen diethyl-nitrosamine, in which DNA damage contributes to necrotic cell death, resulting in an inflammatory action that activates tumor growth [19].…”