Association Between Genetic Polymorphisms Of Cytokines And Biomarkers And Sepsis-induced AKI

Objective:Explore the relationship between the genetic polymorphisms of inflammatory cytokines and biological markers of sepsis induced AKI,for acute kidney injury susceptibility genes and risk assessment of acute kidney injury,early diagnosis,gene therapy and prognosis to provide theoretical basis.Methods:Continuous recruitment of 396 patients with ICU in Zhejiang Province People's Hospital from October 2012 to November 2014.On the research object to within 24 hours after admission to the ICU stays to take the blood and urine specimens,using enzyme-linked immunosorbent assay(ELISA),and the determination of people blood specimens biomarkers(NGAL and KIM-1)and the urine biological signs(IGFBP-7,IL-18,TIMP-2)concentration.At the same time,DNA was extracted from the blood samples of the study,and the SNaPshot method was used for genotyping.We were selected for rs 1800796(rs1946518,rs 187238,rs360719),IL-18 and IGFBP7 rs11573014 rs4075349,TIMP-2 rs8179090 TNF-a(rs1799724,rs1799964,rs1800630),IL-10(rs1800896,rs1800871 and rs1800872,rs1554286)interleukin-6(IL-6)Study on the genetic polymorphisms of several single nucleotide polymorphisms in target sites.Results:In 396 patients,the final development was AKI with 200 patients(group AKI)and 196 patients(non AKI group)with no AKI.Experimental results show that with non AKI patients compared to IGFBP7 and AKI group,TNF-a(rs1800630)CC genotype p<0.007,IL-10(rs1800896)GA+GG genotype p<0.013 rs4075349 AA genotype(P=0.003),IL-18 rs1946518 CC genotype(P<0.001)the frequency increased significantly,the difference is statistically significant.In the multivariate logistic regression analysis,IGFBP7 rs4075349 AA gene type(3.11,95%CI:1.51-6.42),IL-18 rs1946518 CC gene type(OR=2.58,95%CI:1.12-5.9)still is sepsis induced AKI risk factors.In plasma biological marker levels and cytokine gene polymorphism analysis,IL-10(rs1800896)Ga and GG genotypes showed a higher serum creatinine level(respectively 155.5+10.6 mol/L,271+45.9 mol/L;P=0.04).Carry the research object of IGFBP7(rs4075349),etc.A allele showed higher concentrations in the urine of IGFBP7 detection,respectively for the AA type 141+0.13 ng/ml,GA 0.70+0.12 ng/ml,GG type of 0.51+0.21 ng/ml(P=0.002).At the same time also showed higher urine TIMP-2(2.79+0.25 vs 1.66+0.23 vs 144+0.41ng/ml;P=0.003)and interleukin-18(123.1+10.6 vs 100.7+9.87 vs 90.4+17.2 ng/ml;P=0.03)to detect the concentration,the difference is statistically significant.While carrying IL-18(rs 1946518)C allele is correspondingly exhibit higher urine IL-18 detection concentration(CC type 126.1+10.5 vs AC 101.1+10.3 vs.AA type 81.8+13.7ng/ml;P=0.003).The results with statistical difference.Other biological markers showed no significant difference in the levels of the other genes and urinary biology.Conclusion:IL-18 607(rs1946518)CC genotype,IGFBP7 they(rs4075349 AA genotype,TNF-a 863(rs1800630)of the CC genotype,IL-10 of 1082(sepsis and rs1800896)GA+GG gene type induced AKI occurred risk has significant correlation.The genetic polymorphisms of inflammatory cytokines and biomarkers can provide effective value for early diagnosis of AKI induced by sepsis.In order to.further confirm the accuracy of this study,we may need to carry out a long-term follow-up study of the study,and to organize a larger sample size of prospective studies to demonstrate.