| Objective: To explore the relationship between the rs3733402 polymorphism of KLKB1 gene and the level of bradykinin in serum and the development of diabetic nephropathy(DN).Methods: A total of 261 patients with type 2 diabetes mellitus in Shandong Province were collected,including 165 patients with simple diabetes mellitus and 96 patients with diabetic nephropathy.Another 107 healthy people were selected as the normal control group.Sanger sequencing was used to screen the mutation of KLKB1(rs3733402)gene in plasma to explore the relationship between KLKB1 gene mutation and DN.Enzyme linked immunosorbent assay(ELISA)was used to detect bradykinin in serum of all cases collected above,and to study the effect of this index on diabetes or diabetic nephropathy.This study has informed the patients and obtained their informed consent,and was approved by the ethics committee of the multiple medical centers.Results:(1)There is no significant difference in the UA?BUN,LDL-C,HDL-C,TG,TC,FPF,Cr,e GFR,Hb A1 c,SBP,family history,smoke and drink history in the three group(P<0.05).(2)The logistic regression model was used to evaluate the statistical correlation between non genetic factors and diseases(including diabetes mellitus and diabetic nephropathy).The results showed that the risk of the disease was 1.022 times of the original one year old,P = 0.0210;compared with the non-smokers,the former was 2.1318 times of the latter,P = 0.0013.Age,smoke,drink,family,SBP,diff_BP,MAP,EGFR,Cr,FPG and Hb A1 c were related to DM and DN,with statistical difference(P < 0.05).(3)Sanger sequencing results showed that KLKB1 rs3733402 genotypes and alleles had no significant difference among the three groups(P > 0.05).(4)The results showed that the mutation of KLKB1 rs3733402 had no significant correlation with DM and DN(P > 0.05).The results of correlation analysis of serum bradykinin level with DM and DN showed that serum bradykinin level was closely related to the occurrence of DM and DN.There was a statistical difference between BK and DM,DN by ordinal logistic regression model(P<0.05).On the basis of adjusting covariates,BK was statistically correlated with disease.The risk of BK increased by 1 unit was 0.9803 times(P<0.05).(5)The diabetic nephropathy group was divided into three stages of diabetic nephropathy,four stages of diabetic nephropathy and five stages of diabetic nephropathy.The results were still statistically significant(P = 0.0021),indicating that the risk of DN progression to the next stage was 0.9794 times for every 1 ng / ml increase of BK,suggesting that the higher BK,the more difficult DN progression,BK played a protective role in the development of DN(P = 0.0021).(6)The results of logistic regression analysis showed that there was a difference in BK between diabetic nephropathy and control group: the risk of diabetic nephropathy was 0.9651 times when BK increased by 1 unit.The correlation between BK and the stage of diabetic nephropathy was analyzed by logistic regression model(P = 0.012).The correlation between BK and the stage of diabetic nephropathy was analyzed by logistic regression model.The results showed that the increase of BK had protective effect on the stage of microalbuminuria and renal insufficiency.Conclusion: There is no significant correlation between the rs3733402 polymorphism of KLKB1 gene and DN.Serum bradykinin level is related to the occurrence and development of type 2 DM,which is a protective factor of DN. |
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