Genetic Polymorphisms of IFNG, IFNGR1, and Androgen Receptor and Chronic Prostatitis/Chronic Pelvic Pain Syndrome in a Chinese Han Population

Abstract

Background. Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) refers to a common disorder with unclear etiology and unsatisfactory treatment, which reduces the male’s quality of life. Objective. To examine the effects of genetic polymorphisms of IFNG, IFNGR1, and androgen receptor (AR) on CP/CPPS. Methods. The single nucleotide polymorphisms (SNPs) of IFNG, IFNGR1, and AR were genotyped with the improved multiplex ligation detection reaction. The GTEx, RegulomeDB, HaploReg, and 3DSNP databases were adopted to predict the regulatory functions of the genotyped SNPs. The correlation between SNPs and CP/CPPS was analyzed with the ${\chi }^2$ test, logistic regression, and two genetic models (codominant and log-additive models). The nomogram was built to predict the risk of CP/CPPS occurrence. Results. On the whole, 130 CP/CPPS patients and 125 healthy controls were recruited in the study, and 18 SNPs of IFNG, IFNGR1, and AR were genotyped. The results of functional annotation indicated that the 18 genotyped SNPs might have regulatory effects in the whole blood. The rs144488434 was correlated with the elevated CP/CPPS risk (odds ratio (OR): 2.40, 95% confidence interval (CI): 1.12-5.13, ${\chi }^2=5.37$ , and $P=0.021$ ) by the ${\chi }^2$ test. In the built genetic models, rs10457655 was correlated with the elevated National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scores (codominant model: GA/GG: $\text{crude}\text{mean}\text{difference}\left(\text{MD}\right)=0.98$ , 95% CI: -1.71-3.67 and AA/GG: $\text{crude}\text{MD}=9.10$ , 95% CI: 0.58-17.62, $P=0.10$ ). In subgroup analysis, rs2069718 was correlated with the elevated CP/CPPS risk (log-additive model: $\text{crude}\text{OR}=2.18$ , 95% CI: 1.03-4.64, and $P=0.034$ ) in $\text{patients}\ge 35$ years. The nomogram integrating age, rs2069718, rs10457655, and rs144488434 showed good performance to predict the risk of CP/CPPS. Conclusions. Genetic polymorphisms of IFNG, IFNGR1, and AR might act as the genetic factors for CP/CPPS susceptibility, which deserved further explorations.