| Objectives: Growth differentiation factor-15(Growth Differentiation Factor-15,GDF-15)is one of the superfamily members of TGF-?.In recent years,GDF15 has been proved to play an important role in the development and progression of many diseases,including CKD,cancer,diabetes,as well as CVD.Recent studies have suggested that there are multiple single nucleotide polymorphisms(SNP)sites in GDF-15,and rs1058587 plays an important role in amino acid sequence changes,which may affect the occurrence and progression of disease,The G allele of SNP rsl058587 was reported to increase the risk of hypertension mortality of prostate cancer,tumorigenesis,metastasis and prognosis in colorectal cancer.and many studies have shown that changes in serum levels of GDF15 are closely related to many diseases,which are highly expressed in a short period of time under pathological conditions such as stress and inflammation.Recently,Nair demonstrated that after adjusting for potential confounders,the circulating GDF-15 levels strongly correlated with intrarenal expression of GDF15 and significantly associated with increased risk of Chronic Kidney Disease(CKD)progression in two independent cohorts.Circulating GDF15 might be a marker for intrarenal GDF15-related signaling pathways associated with CKD and CKD progression.CKD has received increasing attention as a major public health issue over the past ten years.There are currently 700 million patients with CKD worldwide,more than 130 million people in China,and patients entering hemodialysis and peritoneal dialysis are also on the rise year by year,and the mortality rate of ESRD patients is higher,But the relationship between the variants of GDF15 and the increased risk of mortality for patients with ESRD is still unclear.In this study,we investigated the role of SNP rsl058587 in the susceptibility to the ESRD patients and the risk for the mortality of ESRD patients to provide a basis for the prognosis of end-stage kidney disease.Methods: A total of 296 ESRD patients and 300 healthy individuals were enrolled.All the patients were followed-up for 3 years.The genotype of GDF-15 rs1058587 was determined PCR amplification and Sanger sequencing.Measure blood biochemical index in group population and compare its baseline index,Polymorphic distribution and survival status of GDF-15 gene rs1058587 bits in comparative health group and ESRD group.The baseline serum GDF-15 level was measured by enzyme-linked immunosorbent assay(ELISA).Results:(1)By comparing the baseline characteristics of the health group and the patient,the average age of the ESRD group(n-300,male: 153 female: 143),the health control group(n-300,male:167,female:133),the average age of the control group and the ESRD group was 52.59 ±17.19 years and 52.68 ±12.94 years,respectively.The ESRD group and the control group were comparable in age(P=0.07)and gender(P-0.934).There was a significant difference between blood urea nitrogen,blood creatine and albumin in the two groups(P =0.001).(2)The frequency of G allele of the ESRD group was significantly higher than that of healthy group(30.14% vs.25.17%),In the co-dominant model,there were significant differences between CC,CG and GG genotype frequencies in ESRD group and control group(P-1.04 × 10-3);(3)The baseline characteristics of the three different genotype groups of ESRD patients with ESRD patients GDF-15 single nucleotide site rs1058587 showed no significant difference in age,sex,iPTH,ferritin,Cr,Blood urea nitrogen,serum calcium and serum phosphorus(P>0.05)Significant differences between white blood cells and LDL in three groups(P <0.05)(4)Kaplan-Meier survival analysis showed that the three-year overall survival rate of patients in the GG group was significantly lower than that in the CC group and the CG group(log-rank test,P = 0.027)(Fig.1).Univariate analysis of the cox regression model showed that age > 60 years,total cholesterol > 6 mmol/L,GG genotype of GDF15,and dominant models were significantly associated with the overall survival in ESRD patients.There was no statistically significant association among gender,BMI,low-density lipoprotein,high-density lipoprotein,CRP,Ca,P,Hb,PTH,BUN,hypertension,and recessive models with prognosis(P > 0.05).Multivariate analysis showed that age > 60 years old total cholesterol > 6 mmol/L and GG genotype were independent risk factors for mortality,but the dominant model was not an independent risk factor for prognosis in patients with ESRD(P = 0.192).(5)Total 45 patients with different genotypes were selected for the detection of serum GDF15 concentration by ELISA.The Kruskal-Wallis H-test showed that there was no significant difference in the concentration of GDF15 among the three subgroups of CC,CG and GG(Fig.3).Pearson correlation analysis showed that the correlation coefficients between serum GDF-15 concentration and Cr,BMI and BUN were 0.18,0.12 and 0.13(P > 0.05),respectively.It was suggested that there was no significant correlation between serum GDF15 concentration and Cr,BMI and BUN in patients with ESRD.Conclusion: our results demonstrated that the G allele or CG/GG genotype of GDF15 rs1058587 was associated with higher susceptible risk of ESRD and the genotype GG was an independent risk factor for overall mortality in patients with ESRD. |
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