The Study Of Single Nucleotide Polymorphism With Type 2 Diabetic Kidney Disease

Research BackgroundDiabetic kidney disease(DKD)is one of the most common and serious chronic complications of diabetes.The occurrence and development of DKD not only increases the risk of death and medical expenses for diabetic patients,but also imposes a heavy burden on the family and society.With the successive completion of the "Human Genome Project" and the "Human Genome HapMap Project",the rapid development of the GWAS method,as well as the development of precision medicine research programs,the analysis of single nucleotide polymorphisms(SNPs)of genes has become one of the important research methods for the complex diseases.In recent years,scholars have discovered a series of genetic loci related to DKD.However,there are obvious differences in the genetic characteristics and phenotypes of DKD among different ethnic groups and regions.At the same time,there are some differences in the frequency distribution of the alleles among different ethnic groups.ObjectivesTo detect the genotype distribution of different SNP sites of patients who suffer type 2 diabetes without Diabetic Kidney Disease(NDKD)and who suffer Type 2 Diabetic Kidney Disease(DKD).To explore the relevance between DKD of patients with type 2 diabetes mellitus and SNPs so that can provide more experimental evidence for the prevention and treatment of type 2 diabetic nephropathy.MethodsA number of 187 subjects as research objects were recruited from January 2017 to December 2017 in Zhujiang Hospital of Southern Medical University,among which there were 78 patients(40 females and 38 males)in the NDKD group and 109 patients(45 females and 64 males)in the DKD group.(Every patient has a history of more than 10 years of type 2 diabetes.)Demographic data and clinical biochemical indicators were collected.Ten SNP loci were screened and the genotypes of whole blood SNP loci were detected by matrix-assisted laser desorption/time of flight mass spectrometry(MALDI-TOF).Adopting SPSS20.0 statistical software to analyze the NDKD group and DKD genotype distribution difference,and according to different genetic model of each point genotype distribution statistical analysis,statistically significant difference between the groups loci,further according to the urinary protein creatinine ratio(ACR)in patients with DKD group and glomerular filtration rate(GFR)level subgroup analysis genotype distribution and the relationship between the severity of DKD.Results1.Compared with the NDKD group,the indexes of Urea,Cr,ACR,FPG,and LDL-C in the DKD group increased,and the GFR decreased.The difference between the groups was statistically significant(P<0.05).2.The detection and genotyping of 10 SNP sites were completed.The P values of the rs6128541 site of DKD group and rs646776 site of the NDKD group were all<0.05,which was not representative of the group.3.There were no statistically significant differences in the genotype frequency distributions of rs17428041,rs451041,rs2073618,rs12437854,rs9298190,rs3809346 among the 8 SNPs in the NDKD and DKD groups that met the genetic balance test(P>0.05).There was a statistically significant difference of rs4773144 and rs7588550 in genotype frequency distribution between NDKD and DKD group(P<0.05).4.According to allelic frequencies and genotype frequencies in different genetic models--recessive,dominant,ultra-dominant,co-dominant model,the rs4773144-G allele of COL4A1 and COL4A2 may be the risk allele of DKD(2:18.309,P<0.001,OR:2.521,95%CI:1.643,3.67).The rs4773144-G allele of ERBB4 may be a DKD-protected gene(2:77.474,P<0.001,OR:0.137,95%CI:0.086,0.217).5.The relationship between genotype distribution and ACR,GFR was further analyzed.The genotype distribution frequencies of rs4773144 and rs7588550 were not correlated with ACR as well as GFR levels in the DKD group(P>0.05).ConclusionsThe rs4773144 and rs7588550 polymorphisms are associated with DKD.The rs4773144-G allele may increase the risk of DKD while the rs7588550-G allele may reduce the risk of DKD.The genotype frequencies of rs4773144 and rs7588550 were not significantly different in the subgroups with different ACR and GFR levels in the DKD group,and maybe not significantly related to the severity of DKD.