Correlation Between Single Nucleotide Polymorphisms at the 3'-UTR of the NFKB1 Gene and Acute Kidney Injury in Sepsis.

Abstract

Objective: We aimed to study the relationship between single nucleotide polymorphisms (SNPs) in the 3'-untranslated region of the nuclear factor-kappaB (NF-κB) gene NFKB1 and the risk of acute kidney injury (AKI) in sepsis. Methods: The genotypes of the NFKB1 gene loci rs41275743 and rs4648143 were obtained by Sanger sequencing from 235 AKI patients and 235 non-AKI patients (No AKI). The plasma levels of Homo sapiens (human) microRNAs (hsa-miR)-580, hsa-miR-671-3p, hsa-miR-886-5p, hsa-miR-299-5p, hsa-miR-557, and hsa-miR-9 were determined by quantitative real-time polymerase chain reaction. The P50 protein in lymphocytes and the levels of tumor necrosis factor alpha (TNF-α), serum creatinine (SCr), cystatin (Cys)-C, and kidney injury molecule (KIM)-1 in plasma were detected by enzyme-linked immunosorbent assays. Results: The risk of AKI in patients with sepsis in A-allele carriers of the NFKB1 gene rs41275743 locus was 1.46 times higher than that of the G-allele carriers. The risk of AKI in patients with sepsis in A-allele carriers of the NFKB1 gene rs4648143 locus was 1.56 times higher than that of the G-allele carriers. Acute Physiology and Chronic Health Evaluation (APACHE) III score, Simplified Acute Physiological Score (SAPS) II, Sequential Organ Failure Assessment (SOFA), rs41275743, and rs4648143 were all independent risk factors for AKI. The plasma levels of P50 protein, TNF-α, SCr, Cys-C, and KIM-1 from patients with sepsis carrying the rs11475743 GG and rs4648143 GG genotypes were significantly lower than in those carrying the A-alleles (GA/AA). The levels of hsa-miR-580, hsa-miR-671-3p, and hsa-miR-886-5p in the plasma of patients carrying the rs41275743 GA/AA genotypes were significantly lower than in those with the GG genotype, whereas the levels of hsa-miR-299-5p, hsa-miR-557, and hsa-miR-9 showed no significant difference in patients with different genotypes of the rs41275743 locus. The levels of hsa-miR-299-5p, hsa-miR-557, and hsa-miR-9 in the plasma of patients carrying the GA/AA genotype of the rs4648143 locus were significantly lower than in those with the GG genotype, whereas the levels of hsa-miR-580, hsa-miR-671-3p, and hsa-miR-886-5p did not change significantly in patients carrying different genotypes at the rs4648143 locus. Conclusion: SNPs in the NFKB1 gene loci rs41275743 and rs4648143 are associated with the risk of AKI in patients with sepsis.