Association Of Gene Polymorphisms Of Cytokine And Cytokine Receptor With Chronic Prostatitis/chronic Pelvic Pain Syndrome

PART 1 Follow up of patients with "prostatitis-like symptom"Objective To study the clinical curative effect and prognosis of "prostatitis-like symptom" and the relevant factors affecting the curative results. To select the typical stubbornness chronic prostatitis patient to participate in the second part of laboratory research according to curative effect.Methods 144 cases of "prostatitis-like symptom" patients in our hospital were adopted from June, 2004 to September, 2004. All the patients received the investigation based on NIH-CPSI questionnaire. Expressed prostatic fluids(EPS) were acquired and prostatic fluid routine inspection were executed. Patients were classified based on white blood cell count in EPS according to the NIH1995 standard classification, and accepts the recommendated treatment. Patients received follow-up visit after 6 weeks and 1 year respectively.Results After 6 week regular treatment, 115 patients continued to participate in the research. Convalescing rate of the 115 "prostatitis-like symptom" patients was only 13.9%. 51.3% patients obtained the varying degree of alleviation of symptoms or the condition changed for the better.34.8% patients' symptoms did not have a improvement or the condition aggravated. Curative effect of "prostatitis-like symptom" had nothing to do with the age, the course of illness, neither with whether there was the mycoplasma or the chlamydia as well as white blood cell number in EPS.ⅢA Type andⅢB Type "prostatitis-like symptom" may had the interconversion during patient's course of treatment. Situation was common byⅢA change to theⅢB, and less wasⅢB to theⅢA.Conclusions Combining the NIH-CPSI questionnaire survey with clinical basic inspections-prostate gland fluid routine inspection and the bacilli culture help to make a clinical diagnosis of prostatitis. "prostatitis-like symptom" was still a difficult problem in clinical aspect, with the amelioration rate and convalescing rate was low. Interconversion existed between two types of "prostatitis-like symptom" during the course of disease, which was meaningful in the case of analyzing scientific research data about chronic prostatitis. PART 2 Association of gene polymorphisms of cytokine and cytokine receptor with chronic prostatitis/chronic pelvic pain syndromeObjective: To research the distribution of gene polymorphisms of cytokines and cytokine receptors in CP/CPPS patients group and health control group. To explore the role of gene polymorphism of cytokine and cytokine receptor in CP/CPPS and their role in diagnosis and treatment of CP/CPPS.Methods: We have genotyped 24 patients diagnosed with typical CP/CPPS which selected from research of part one and 51 health controls from the Han nationality population in Hunan province for the single nucleotide polymorphisms of 13 cytokines at 22 site: IL-lα-889 C/T,IL-1β(-511 C/T,＋3962C/T),IL-1RPst 1970 C/T, IL-1Ra mspⅠ11100 C/T,IL-4Rα＋1902 A/G,IL-12-1188 A/C,IFN-γUTR5644 A/T,TGF-β1 (codon10 C/T,codon25 C/G),TNF-α(-308 A/G,-238 A/G),IL-2 (-330 T/G,＋166G/T),IL-4 (-1098 G/T,-590 C/T,-33C/T),IL-6 (-174 C/ G,nt565 A/G),IL-10 (-1082 A/ G,-819C/T,-592 A/C). Clinical data were collected on all patients. DNA was extracted with BioGene-Expuze 10 DNA kit supplied by Texas BioGene Incorporation. Genotyping was carried out using SSP-PCR technique with cytokine genetyping kit supplied by PEL-FREEZ Incorporation. IL-10 level in peripheral blood of 51 health controls and in EPS of 20 CP/CPPS patients were tested using ELISA technique.Results:1.The frequency of G allele (2.1% in patients group, 4.9% in health control group) of IL-10 at -1082 was lower than that of A allele(97.9% in patients group, 95.1% in health control group) obviously in Han nationality population. There were no significant difference of allele frequencies between patients group and health control group.2.A statistically significant difference was observed in the genetype frequency of the polymorphisms between the group of patients and the group of healthy individuals with the polymorphism of the IL-10 at -1082,where frequency of T/T genetype was higher in patient group(62.5% vs 31.3%,p＜0.05). A statistically significant difference was observed in the genetype frequency of the polymorphisms between the group of patients and the group of healthy individuals with the polymorphism of the IL-10 at -592, where frequency of A/A genetype was higher in patient group(62.5% vs 31.3%,p＜0.05).3.A statistically significant difference was observed in the allele frequency of the polymorphisms between the group of patients and the group of healthy individuals with the polymorphism of the IL-10 at -819, where frequency of T allele was higher in patient group(75.0% vs 55.9%,p＜0.05). A statistically significant difference was observed in the allele frequency of the polymorphisms between the group of patients and the group of healthy individuals with the polymorphism of the IL-10 at -592, where frequency of A allele was higher in patient group(75.0% vs 55.9%,p＜0.05).4.A statistically significant difference was observed in the genetype frequency of the polymorphisms between the group of patients and the group of healthy individuals with the polymorphism of the IL-10 at -1082,-819,-592, where frequency of ATA/ATA genetype was higher in patient group (62.5% vs 31.2%,P＜0.05 )5.There were no statistically significant association of distribution of genetype frequency with age, course, CP/CPPStype (ⅢA/ⅢB) and neither with score of pain, pain degree, pain after ejaculation, symptom with void, pain during void, objective symptom, quality of life according to NIH-CPSI questionnaire.6.The IL-10 level in peripheral blood of ACC/ACC group and GCC/ATA＋GCC/ACC group were statistically significantly different from that of ATA/ATA group(256.8±209.7 pg/ml, 355.2±298.4 pg/ml, 110.7±102.6 pg/ml,respectively). Level of IL-10 in ATA/ACC group was higher than that in ATA/ATA group, however the difference was not significant.7.Gene polymorphism at -1082,-819,-592 of IL-10 have no statistically significant association with levels of IL-10 in EPS of CP/CPPS patients. 8. Genetype T/C of IL-4 at -590 was found more frequently in the patients (50.0% vs 27.5%), while the difference was not statistically significant,with P value was 0.056 that was cloes to the critical value.9. There was no statistically significant difference observed between healthy group and patients group on other researched gene polymorphisms.10. No statistically significant difference was observed in the haplotype frequency and genetype frequency of TGFβgene (codon 10, condon 25) and TNFαgene (-308, -238) between the CP/CPPS patients and the healthy control group.Conclusions: Our data suggested that anti-inflammation cytokine gene polymorphisms but not proinflammation cytokine gene polymorphisms were associated with the pathogenesis of CP/CPPS. IL-10 gene polymorphism prearranged the level of IL-10 in peripheral blood. Low product genetype of IL-10 was more frequently obserbed in CP/CPPS population. Frequency of allele G of IL-10 at -1082 was significantly lower in Han nationality population than that in Caucasians. Gene polymorphisms of IL-10 at -1082 cann't establish its role in pathogenesis of CP/CPPS, however gene polymorphisms of IL- 10 at -819 and at -592, which were linkage with site -1082, can play its role in etiology of CP/CPPS. Gene polymorphism of IL-10 cann't prearrange the level of IL-10 in EPS of CP/CPPS patients. Analysis of gene polyphisms of cytokine help the patient to accepte a individual treatment in consideration of humanity.