Associations Between Genetic Polymorphisms Of Chemokines And Chemokine Receptors And Benign Prostatic Hyperplasia

Objective: It has been increasingly recognized that chemokines and chemokine receptors play an important role in the occurrence and progression of prostate diseases due to their functions as mediator in the inflammatory response.In this study we aimed to assess the associations between single nucleotide polymorphism(SNP)of CCL2,CCR2,CCL5 and the occurrence and progression of benign prostatic hyperplasia(BPH).Methods: A total of 109 patients with BPH and 160 normal controls were included.Technique methods of polymerase chain reaction-ligase detection reaction(PCR-LDR)were used to genotype the genetic polymorphisms of CCL2 rs1024611,CCR2 rs1799864,CCL5 rs2107538 and their associations with BPH risk were evaluated.Principal Findings: 1.The genotype and allele frequency of CCL2 rs1024611 and CCR2 rs1799864 distributed between BPH group and control group were not statistically significant.The G/A genotype and A allele frequency of CCL5 rs2107538 were significantly lower in the BPH group than in the control group(39.5% vs.54.4%,OR = 0.37,95% CI = 0.17-0.78,p = 0.01;32.6% vs.41.6%,OR=0.58,95%CI=0.35-0.96,p=0.033),which can reduce the risk of BPH.2.In the joint analysis of every two groups,it was found that the combined genotype G/A-A/G of CCL5 rs2107538 and CCL2 rs1024611 showed a decreased risk of BPH(OR=0.20,95% CI=0.05-0.77,p=0.019).But the G/G-G/G combination had suggested a increased risk of BPH(OR=10.83,95%CI=1.50-78.13,p=0.018).Combined genotype G/A-G/G of CCL5 rs2107538 and CCR2 rs1799864 also demonstrated a protective factor for BPH(OR=0.29,95% CI=0.11-0.78,p=0.014).3.The associations between this 3 SNPs and the clinicopathological characteristics of BPH parents were further analyzed.CCL5 rs2107538 was associated with prostate volume(PV),reflecting an increasing effect on the risk of large PV(PV ≥ 30 mL)progression for BPH patients with G/A genotype and A allele(OR=3.02,95% CI=1.28-7.11,p=0.011;OR=1.94,95% CI=1.08-3.49,p=0.027).CCR2 rs1799864 was associated with International Prostate Symptom Score(IPSS)and maximum urinary flow rate(Qmax).BPH patients with the A allele were protected from progressing to higher IPSS(IPSS ≥ 20)(OR=0.43(95%CI=0.20-0.90,p=0.024),and patients with the G/A genotype were less likely progressing to lower Qmax(Qmax<10mL/s)(OR=0.38,95% CI=0.16-0.92,p=0.031).However,there was no significant correlation between CCL2 rs1024611 and BPH progression.Conclusion: CCL5 rs2107538 was significantly associated with both the occurrence and progression of BPH.CCR2 rs1799864 may also play a role in the progression of BPH.However,no association of CCL rs1024611 was observed with BPH risk.