Department of Internal Medicine, Aging and Renal Diseases, University of Bologna, Bologna, Italy.
Transplantation. 2010 Apr 27;89(8):1001-8. doi: 10.1097/TP.0b013e3181ce243f.
Cardiovascular disease (CVD) represents the main cause of morbidity and mortality after renal transplantation. In view of the modern paradigm of atherosclerosis as an inflammatory disease, this study investigated the impact of inflammatory cytokine polymorphisms on posttransplant CVD.
The association between cytokine polymorphisms and CVD was assessed in a case-control study to identify the differences in genotype distributions between kidney allografts with or without posttransplant CVD. To validate our results in two independent groups, we divided a cohort of 798 renal transplant recipients according to geographic area: an evaluation cohort of 478 patients from Emilia-Romagna and a validation cohort of 320 patients from the rest of Italy. Tumor necrosis factor (TNF)-alpha, transforming growth factor-beta1, interleukin (IL)-10, IL-6, interferon-gamma, and IL-8 polymorphisms were analyzed, and thereafter, the cytokine production genotype was assigned.
In the evaluation cohort, the patients in the CVD and no-CVD groups differed significantly in TNF-alpha and IL-10 genotype frequencies. Using multivariate analyses to test the association with CVD, the TNF-alpha high-producer genotype was associated with a significantly increased cardiovascular risk (odds ratio [OR]=4.41, 95% confidence interval (CI)=2.53-7.67). Conversely, the IL-10 high-producer genotype resulted protective against CVD (OR=0.07, 95% CI=0.02-0.29). These findings were confirmed in the validation cohort where the carriers of the TNF-alpha high-producer genotype proved to be at 2.45-fold increased cardiovascular risk (OR=2.45, 95% CI=1.29-4.63), whereas the IL-10 high-producer genotype was associated with a 0.08-fold reduced risk (OR=0.08, 95% CI=0.02-0.36).
This work suggests a prognostic value of TNF-alpha and IL-10 genotypes, which might represent cardiovascular risk markers in renal transplant.
心血管疾病（CVD）是肾移植后发病率和死亡率的主要原因。鉴于动脉粥样硬化作为一种炎症性疾病的现代模式，本研究探讨了炎症细胞因子多态性对移植后 CVD 的影响。
在病例对照研究中评估细胞因子多态性与 CVD 的关系，以确定移植后发生 CVD 的肾移植和未发生 CVD 的肾移植之间基因型分布的差异。为了在两个独立的群体中验证我们的结果，我们根据地理区域将 798 例肾移植受者分为一个评估队列（478 例患者来自艾米利亚-罗马涅大区）和一个验证队列（320 例患者来自意大利其他地区）。分析肿瘤坏死因子（TNF）-α、转化生长因子-β1、白细胞介素（IL）-10、IL-6、干扰素-γ和 IL-8 多态性，然后分配细胞因子产生基因型。
在评估队列中，CVD 组和无 CVD 组的 TNF-α和 IL-10 基因型频率差异显著。使用多元分析检验与 CVD 的关联，TNF-α高产生基因型与心血管风险显著增加相关（比值比[OR]=4.41，95%置信区间[CI]=2.53-7.67）。相反，IL-10 高产生基因型对 CVD 具有保护作用（OR=0.07，95%CI=0.02-0.29）。这些发现在验证队列中得到了证实，其中 TNF-α高产生基因型的携带者患心血管疾病的风险增加了 2.45 倍（OR=2.45，95%CI=1.29-4.63），而 IL-10 高产生基因型的携带者患心血管疾病的风险降低了 0.08 倍（OR=0.08，95%CI=0.02-0.36）。
本研究提示 TNF-α和 IL-10 基因型具有预后价值，可能是肾移植患者的心血管风险标志物。
