No Association of TGF-beta Gene Polymorphism with the Progression of Autosomal Dominant Polycystic Kidney Disease(ADPKD) in Korean Patients / 대한신장학회잡지

BACKGROUND: Two genetic loci, PKD1 and PKD2, have been identified as being responsible for ADPKD, and PKD1 is known to be associated with poor prognosis. However, the presence of intrafamilial clinical diversity suggests the presence of disease-modifying loci. Because the mechanism of renal failure in ADPKD includes cystic growth and tubulointerstitial atrophy and fibrosis, we studied the associations between two cytokine gene polymorphisms in the TGF-beta gene, which are known to be related with chronic tubulointerstitial inflammation, and ADPKD progression in Korean patients. METHODS: 47 normal controls and 114 individuals with ADPKD were genotyped by PCR-RFLP, and the TGF-beta gene leader sequence of T869C(Leu10Pro) variant was compared with MspA1I and G915C (Arg25Pro) with BglI. Statistic significances were determined using the Chi-square test. RESULTS: The distribution of alleles for the TGF-beta Leu10Pro polymorphism in ADPKD was : T 52%, C 48%, which was similar to the Korean(56 : 44, p= 0.670) and Western controls(65 : 35), and in addition, no differences were found between the CRF and the non-CRF groups(p=0.571) or the early hypertension and the normotension groups(p=0.252). The distribution of alleles for the TGF-beta Arg25Pro polymorphism was all GG type, which was different from Western controls(90 : 10, p=0.000). CONCLUSION: Our results suggest that the polymorphism at Arg25Pro of TGF-beta in Korean population has different allele distribution from Western, and the polymorphism at Leu10Pro of TGF-beta has no association with the renal progression of Korean ADPKD patients.

Cytokine Profile in the Aspirated Cystic Fluids in Autosomal Dominant Polycystic Kidney Disease (ADPKD) Patients / 대한신장학회잡지

BACKGROUND: The pathogenesis of ADPKD is still unknown but the proliferation of cystic epithelia and the fluid secretion to cystic lumen are thought to be important. Cytokines play a pivotal role in growth, differentiation, and apoptosis in general, but there were few reports about the cytokine profile in ADPKD cysts. METHODS: In this study, we measured cytokine content in aerobic culture-negative cystic fluids from 23 patients with symptomatic normal to end-stage (n=3) ADPKD in order to elucidate the possibility that cytokines are related to the development and progression of disease. Enzyme-linked immunosorbent assays (ELISAs) were used to detect IL-1beta, IL-2, IL-4, IL-6, IL-10, and IFN-gamma with commercial kits. RESULTS: Male to female ratio was 6 : 17 and the median age at examination was 52 years (range 36 to 78). IL-1beta was present in 18 of 23[78%] (11 to 173 pg/mL), IL-2 in 18 of 23[78%] (5 to 159 pg/ mL), IL-4 in 9 0f 23[39%] (8 to 156 pg/mL) and IL-6 in 10 of 23[43%] (16 to 1498 pg/mL). IL-10, and IFN-gamma were not detected. IL-1beta concentrations correlated directly with those of IL-2 (r=0.7671). IL- 6 levels in patients with azotemia (n=7) [288.4+/-26.2 (mean+/-S.D.)] were significantly higher than those of normal renal function group (98.3+/-413.9)(p<0.01). Such difference was not found in other cytokines. Cytokine concentrations did not correlate with sodium concentrations, nor with cystic fluid osmolality, indicating that differences in concentrations among fluids could not be explained by differences in water content. And, there was no significant correlation between the intracystic concentrations of these cytokines and the corresponding cyst diameters. CONCLUSION: These data identify proinflammatory cytokines as possible mediators to the morbidity of ADPKD. Especially, IL-6 levels of cystic fluid were elevated in the azotemic ADPKD patients.