Search

ABSTRACT Aim: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) can counteract inflammation and atherosclerosis, both common causes of morbidity in peritoneal dialysis (PD) patients. We examined the relation between serum soluble TRAIL (sTRAIL) levels and the outcome of Chinese PD patients. Methods: We studied 116 new PD patients (67 males, age 56.7 ± 13.4 years). Baseline serum sTRAIL level was determined and grouped to tertiles 1 (lowest) to 3 (highest). All patients were followed for 20.9 ± 7.0 months. Results: Patient survival was 83.4%, 74.2% and 100% for tertiles 1 to 3, respectively, at 24 months ( P = 0.021). Multivariate Cox regression analysis showed that serum sTRAIL level was an independent predictor of patient survival after adjusting for confounding factors (adjusted hazard ratio 0.962, 95% confidence interval [CI] 0.935-0.991, P = 0.010). Conclusion: A higher baseline serum sTRAIL level was associated with a better survival of PD patients. The detailed mechanism deserves further investigation. [ABSTRACT FROM AUTHOR]

Summary: Background/Purpose: Human oxoguanine-DNA glycosylase 1 (hOGG1) is the enzyme that has DNA repairing capacity. C1245 G substitution of the hOGG1 gene results in reduced enzyme activity. Peritoneal dialysis (PD) is known to cause oxidative DNA damage. We investigated the effect of hOGG1 polymorphism on the clinical outcomes of PD patients. Methods: We studied the hOGG1 polymorphism in 441 new PD patients (232 men, age 56.6±13.5 years). The patients were followed for 41.4±18.2 months for cardiovascular events. Results: For the entire cohort, there was no significant difference in the 5-year event-free survival between the CC and CG/GG groups (42.9% vs. 33.2%; p =0.1). However, for patients with baseline serum C-reactive protein (CRP) levels ≤ 5.0mg/L, 5-year event-free survival of the CC group was significantly better than that of CG/GG group (50.3% vs. 31.9%, p =0.046). Multivariate analysis showed that hOGG1 polymorphism was an independent predictor of the survival (p =0.008). In contrast, for patients with baseline CRP > 5.0mg/L, there was no significant difference in 5-year event-free survival between the CC and CG/GG groups (26.7% vs. 30.2%, p =0.9). Conclusion: In PD patients with no systemic inflammation, hOGG1 1245CC genotype confers a survival benefit as compared to CG or GG genotype, but the protective effect disappears in patients with systemic inflammation. Our results suggest a complex interaction between hOGG1 and inflammation in the pathogenesis of cardiovascular disease in PD patients. 背景: 人類oxoguanine-DNA glycosylase 1 (hOGG1)是一種具DNA修復能力的酵素，其酵素活動在hOGG1基因的C1245G替換後會有所下降。此外，腹膜透析(PD)已知會導致DNA的氧化性損害。本研究調查了hOGG1多態性對PD患者的影響。 方法: 研究人員對441位剛開始接受PD的病人(男232人, 年齡56.6 ± 13.5歲)，作出hOGG1多態性的調查，並對心血管事件的發生進行共41.4 ± 18.2個月的追蹤。 結果: 在整體病人中，CC與CG/GG組別之間在5年無事件存活率上無明顯差異(42.9% vs. 33.2%, p = 0.1)；然而，在基線血清C-反應蛋白(CRP)水平 ≤ 5.0 mg/L的病人中，CC組的5年無事件存活率明顯高於CG/GG組(50.3% vs. 31.9%, p = 0.046)。多變數分析顯示，hOGG1多態性是存活的獨立預測因子(p = 0.008)。相反，在基線CRP > 5.0 mg/L的病人中， CC與CG/GG組別之間在5年無事件存活率上並無明顯差異(26.7% vs. 30.2%, p = 0.9)。 結論: 在不具系統性發炎的PD患者間，相比於CG或GG基因型，hOGG1 1245CC基因型具備若干的存活效益，但其效益並未出現於系統性發炎患者間。這些結果意味著，在PD患者的心血管致病過程中，hOGG1與發炎之間存在著複雜的交互關係。 [Copyright &y& Elsevier]

Aim: Interleukin-18 (IL-18) is a pro-inflammatory cytokine and possibly plays an important role in the pathogenesis of cardiovascular disease. The relationship between two IL-18 gene polymorphisms, namely C-607A and G-137C, and cardiovascular disease in patients with diabetic nephropathy was examined. Methods: Two hundred and twenty patients (91 male) with diabetic nephropathy were studied. The IL-18 promoter genotypes were determined. All patients were then prospectively followed for the cardiovascular events. Cardiovascular mortality and all-cause mortality were also compared. Results: Mean age was 64.3 ± 10.6 years; average follow up was 73.9 ± 33.6 months. The frequencies of CC, CA and AA genotypes of the C-607A polymorphism were 25.5%, 48.2% and 26.8%, respectively; GG, GC and CC genotypes of the G-137C polymorphism were 71.8%, 25.0% and 3.2%, respectively. Neither of the polymorphisms were associated with the development of primary cardiovascular end-point. Cardiovascular survival was 84.8% and 70.6% at 60 months for GG and GC/CC genotypes of the G-137C polymorphism, respectively ( P = 0.027); the corresponding actuarial survival was 69.0% and 54.8%, respectively ( P = 0.053). However, the G-137C genotype was not an independent predictor of cardiovascular or actuarial survival after adjusting for confounders by multivariate analysis with the Cox model. The C-607A polymorphism had no significant effect on cardiovascular or actuarial survival. Conclusion: The G-137C polymorphism of the IL-18 promoter is associated with the cardiovascular mortality, and a trend of association with all-cause mortality, in patients with diabetic nephropathy. The association, however, becomes insignificant after adjusting for confounding factors. Further studies are needed to test other genetic determinants of the association between systemic inflammation and cardiovascular disease in renal failure patients. [ABSTRACT FROM AUTHOR]