Association Of Interleukin-6 Gene Polymorphisms And Serum、Urinary Interleukin-6 Levels With The Occurrence And Progression Of Diabetic Kidney Disease In A Northern Han Chinese Population

Objective: We aimed to analyze serum and urinary interleukin-6(IL-6)levels,and IL-6gene polymorphisms in patients with diabetes mellitus(DM),diabetic kidney disease(DKD),and clinical indicators of DKD in a northern Han Chinese population,and to provide a theoretical basis for early identification and treatment of susceptible individuals for DKD.Methods: In this study,a total of 254 eligible examiners who visited the Department of Endocrinology,Department of Nephrology,and physical examination center of the First Affiliated Hospital of China Medical University from July 2019 to June 2021,were examined for serum and urinary IL-6 levels,and the serum and urinary IL-6 levels of were compared among different albumin excretion groups.The polymorphisms of IL-6rs1800795,rs1800796,and rs1524107 were examined in 183 of these subjects,and the associations between genotypes and IL-6 and clinical parameters were analyzed.Results: The level of serum IL-6 in diabetic patients with normal albuminuria was 2.87 ±2.87 pg / ml,which was significantly higher than that in healthy controls(P = 0.002).The urine IL-6 level in the massive albuminuria group was 26.39 ± 42.88pg/ml,which was significantly higher than that in the other three groups(P < 0.001).Serum and urine IL-6levels were positively correlated with urinary microalbumin(MA)and serum creatinine(SCR)(P < 0.001),and negatively correlated with serum albumin(ALB)and estimated glomerular filtration rate(e GFR)(P < 0.001).The sensitivity of serum IL-6 in the diagnosis of DKD was the highest(91%),the specificity of serum and urine IL-6 in the diagnosis of DKD was the highest(81.1%),the joint diagnostic tag =(serum IL-6)+(urine IL-6)* 0.114/0.241,and the cut-off value was 4.45.There were 3 GG,180 GC and 0 CC genotypes in rs1800795.There was no significant difference in genotype and allele frequency of rs1524107 and rs1800796 among healthy control group,DM without DKD group and DKD group(P > 0.05).The serum IL-6 of 183 subjects with rs1524107 CC genotype and rs1800796 GG genotype was 9.81 ± 7.85pg/ml,which was significantly higher than that of CT and GC genotypes.In DKD group,serum IL-6 of rs1524107 CC genotype was higher than TT genotype(P = 0.002);serum IL-6 of rs1800796 GG genotype was higher than CC genotype(P = 0.001),serum IL-6 of rs1800796 GC genotype was higher than CC genotype(P = 0.032).The or value of hypertension was 30.75(95% CI: 13.321-70.991,P < 0.001)and that of smoking was3.51(95% CI: 1.190-10.323,P = 0.023).Conclusion: The increase of serum and urine IL-6 levels in patients with DM and DKD is related to the occurrence and progression of DKD.Combined detection of serum and urine IL-6 is expected to be a biomarker for early diagnosis of DKD.The serum IL-6levels of rs1524107 CC and rs1800796 GG genotype carriers were increased.The synergistic effect of hyperglycemia and rs1524107 CC and rs1800796 GG could further increase the secretion of IL-6,increase the susceptibility of DKD,and further aggravate DKD.Smoking and hypertension are risk factors for DKD.