Supplementary Material for: Gene Polymorphisms of Interleukin-10 and Tumor Necrosis Factor-α Are Associated with Contrast-Induced Nephropathy

<b><i>Background/Aims:</i></b> Contrast-induced nephropathy (CIN) is the third most common cause of hospital-acquired acute renal failure. However, the pathogenesis of CIN remains unclear. This study evaluated the role of anti-inflammatory cytokine interleukin-10 (IL-10) and pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) gene polymorphisms as CIN susceptibility markers after percutaneous coronary intervention (PCI). <b><i>Methods:</i></b> Four IL-10 tag SNPs (rs1554286, rs3021094, rs3790622, rs1800896) and three TNF-α tag SNPs (rs1799964, rs1800630, rs1800629) were analyzed by MALDI-TOF mass spectrometry in 53 CIN patients and 455 control subjects. Serum IL-10 and TNF-α were detected using ELISA. <b><i>Results:</i></b> When compared to controls, the CIN patients showed increased frequencies of CC (rs1554286) and AG+GG (rs1800896) genotypes in IL-10 and GA+AA (rs1800629) genotype in TNF-α (OR = 2.24 (1.13–4.44), p = 0.018; OR = 2.61 (1.30–5.26), p = 0.005, and OR = 2.11 (1.08–4.09), p = 0.025, respectively). Baseline serum IL-10 levels in CIN patients were significantly lower (1.02 ± 1.14 vs. 2.78 ± 4.73 pg/ml, p = 0.008). Patients with CIN had a higher rate of decline in renal function than those without CIN (0.89 ± 1.67 vs. 0.30 ± 0.95 ml/min/1.73 m² per month, p = 0.002). Significantly higher rates of decline in creatinine clearance were noted in patients with TNF-α (rs1800629) GA+AA than GG genotype (0.88 ± 1.83 vs. 0.36 ± 0.70, p = 0.03), and with IL-10 (rs1800896) AG+GG than AA genotype (1.28 ± 2.14 vs. 0.33 ± 0.90, p &lt; 0.001). <b><i>Conclusions:</i></b> Gene polymorphisms of IL-10 and TNF-α are associated with CIN risk and long-term renal outcome after PCI. More prospective studies are needed to confirm our results.

<b><i>背景与目的：</i></b> 造影剂肾病（Contrast-induced nephropathy, CIN）是医院获得性急性肾衰竭的第三大常见病因，但其发病机制尚未明确。本研究旨在探讨抗炎细胞因子白细胞介素-10（interleukin-10, IL-10）与促炎细胞因子肿瘤坏死因子-α（tumor necrosis factor-α, TNF-α）的基因多态性作为经皮冠状动脉介入治疗（percutaneous coronary intervention, PCI）后造影剂肾病易感标志物的价值。
<b><i>方法：</i></b> 本研究采用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF mass spectrometry）技术，对53例造影剂肾病患者与455例对照受试者的4个白细胞介素-10标签单核苷酸多态性（tag SNPs：rs1554286、rs3021094、rs3790622、rs1800896）及3个肿瘤坏死因子-α标签单核苷酸多态性（tag SNPs：rs1799964、rs1800630、rs1800629）进行分型检测；采用酶联免疫吸附试验（ELISA）检测受试者血清中白细胞介素-10与肿瘤坏死因子-α的水平。
<b><i>结果：</i></b> 与对照组相比，造影剂肾病患者的白细胞介素-10基因位点rs1554286的CC基因型、rs1800896的AG+GG基因型，以及肿瘤坏死因子-α基因位点rs1800629的GA+AA基因型频率均显著升高（比值比OR分别为2.24[95%置信区间1.13~4.44]，p=0.018；2.61[1.30~5.26]，p=0.005；2.11[1.08~4.09]，p=0.025）。造影剂肾病患者的基线血清白细胞介素-10水平显著低于对照组（1.02±1.14 vs 2.78±4.73 pg/ml，p=0.008）。造影剂肾病患者的肾功能下降速率显著高于非造影剂肾病患者（0.89±1.67 vs 0.30±0.95 ml·min⁻¹·1.73m⁻²·月⁻¹，p=0.002）。携带肿瘤坏死因子-α基因rs1800629位点GA+AA基因型的患者，其肌酐清除率下降速率显著高于GG基因型携带者（0.88±1.83 vs 0.36±0.70，p=0.03）；携带白细胞介素-10基因rs1800896位点AG+GG基因型的患者，其肌酐清除率下降速率也显著高于AA基因型携带者（1.28±2.14 vs 0.33±0.90，p<0.001）。
<b><i>结论：</i></b> 白细胞介素-10与肿瘤坏死因子-α的基因多态性与经皮冠状动脉介入治疗后造影剂肾病的发病风险及长期肾功能预后相关。未来需开展更多前瞻性研究以验证本研究结果。