Gene polymorphisms of interleukin-10 and tumor necrosis factor-α are associated with contrast-induced nephropathy.
OBJECTIVE
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).


METHODS
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.


RESULTS
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 m(2) 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 < 0.001).


CONCLUSIONS
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.
School of Medicine, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
Chao-Fu
CF
Chang
Tse-Min
TM
Lu
Wu-Chang
WC
Yang
Shing-Jong
SJ
Lin
Chih-Ching
CC
Lin
Ming-Yi
MY
Chung
D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced* / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D015415:Biomarkers; D016022:Case-Control Studies; D016001:Confidence Intervals; D003287:Contrast Media / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D005260:Female; D005787:Gene Frequency; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*
D015415:Biomarkers; D003287:Contrast Media; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D003404:Creatinine