Association Of CUBN Gene Polymorphisms With Type 2 Diabetic Kidney Disease

Background: Diabetic kidney disease(DN)is one of the most serious chronic vascular complications of diabetes mellitus(DM),which has become an important factor leading to the increase of mortality in end-stage renal disease and diabetes mellitus.Recent studies have shown that long-term glucose metabolic disorders and genetic factors are the main causes of DKD.Recently,a genome-wide analysis of 63153 people from Europe and the United States and found that the receptor gene of intrinsic factor vitamin B12 complex is a candidate gene for DKD.The CUBN gene mutation was confirmed by the other two studies in a large sample of European and American Studies with DKD.However,the association between CUBN gene mutation and susceptibility to DKD in Chinese population has not been studied.Due to different geographical and ethnic differences in genetic and phenotypic distribution of DKD,the allele frequencies of single nucleotide polymorphism may be different in another populations,so it is necessary to investigate the association between China population and CUBN gene.Objective: 1.To investigate the distribution of CUBN locus rs1801239(T→C)and rs10795433(A/C)polymorphism in Chinese Han population with type 2(T2DM)diabetes mellitus.2.to investigate the rs1801239(T→C)mutation and rs10795433(A/C)polymorphism of CUBN gene with the susceptibility of DKD.3.Investigate the risk factors of DKD.Methods: Using matrix-assisted laserdesorption ionization time-of-flight mass spectrometry(MALDI-TOF-MS)for genotyping,detection distribution of the CUBN gene rs1801239(T→C)and rs10795433(A/C)in 600 China Han population in T2 DM.Base on urinary albumin excretion rate(UAER),the subjects were divided into two groups:diabetic kidney disease(DKD+)and diabetic without kidney disease(DKD-).The clinical variables,allele frequencies and genotype frequencies of the two groups were compared and analyzed by SPSS16.0 statistical software.Results: 1.Clinical data analysis of the two groups: The total of 600 cases were included,of which the DKD+334cases,the DKD-group of 266,the age of the group were 59.36 ± 10.43 years old and the age of 60.01 ± 12.16.The course of diabetes 、triglyceride level、incidence of hypertension,、systolic blood pressure、diastolic blood pressure and retinopathy were significantly higher in group DKD+ than those in group DKD-,and eGFR in group DKD+ was lower than that in group DKD-2.The frequency distribution of CUBN two variant sites of CUBN : CUBN rs1801239(T→C)(mutation),the 1 genotype was CT,and the other 599 were TT,which showed that the all research object was no variation.CUBN rs10795433 A/C(SNP)genotype measured values and predicted values were not statistically significant differences between(P > 0.05),the two group with Hardy-Weinberg’s law of genetic equilibrium;There were no statistically significant(P > 0.05)between DKD+ group and DKD-group of genotype and allele frequencies Logistic regression analysis of DKD related factors: the expression of rs10795433 A allele or C allele was not a risk factor for DKD.The history of retinopathy,history of ACEI/ACE uesd,systolic blood pressure,triglyceride and total cholesterol were the risk factors of DKD,and the increase of eGFR was the protective factor.Conclusion:1.In this trial,CUBN rs1801239(T→C)have no variation;CUBN rs10795433(A/C)genotype distribution with Hardy-Weinberg’s law of genetic equilibrium.2.In this trial,there was no correlation between rs1801239(T-C)mutation and rs10795433(A/C)polymorphism and DKD polymorphism.However,the close relationship between Cubilin receptor and proteinuria needs to be further expanded to study these two loci.3.In this trial,logistic regression analysis showed that the expression of rs10795433 A allele or C allele was not a risk factor for DKD.Thecourse of diabetes,triglyceride,high blood pressure,systolic blood pressure,diastolic blood pressure and retinopathy increased with the occurrence of DKD,while the increase of eGFR was the protective factor.The results showed that the patients with DKD had the above risk,they should control blood lipid,blood pressure,check the fundus and avoid the use of nephrotoxic drugs.