| Objective:To investigate the relationship between ADP-ribosylation-like factor 15(ARL15)gene single nucleotide polymorphisms(SNPs)rs35941,rs26770,rs4311394,rs6450176,and type 2 diabetes mellitus(T2DM)and diabetic nephropathy(DN)in the Korean and Han populations in Yanbian region.Methods:A case-control design was used to collect 268 patients with normal glucose tolerance in the control group(NGT)(131 Korean,137 Han),393 patients in the type 2 diabetes mellitus group(T2DM)(188 Korean,205 Han),and 90 patients in the DN Group(35 Korean,55 Han).Sequencing and typing the samples;using enzyme-linked immunosorbent assay(ELISA)to detect serum ARL15 levels and adiponectin(PA)in appeal samples;collecting physiological indicators of the samples,such as age and blood pressure,and calculating based on weight and height Body mass index(BMI),biochemical indicators were used to detect various biochemical indicators.Linkage disequilibrium(LD)was used to screen ARL15 gene tag SNPs(TagSNP).Result:1.Results of linkage disequilibrium analysis:LD maps were drawn for the D’and r2 values of the four SNPs(rs35941,rs26770,rs4311394,rs6450176)of the ARL15 gene,which showed that The results show that there is a strong linkage disequilibrium between rs4311394 and rs6450176(D’=0.897,r2=0.780),and a weak linkage disequilibrium with rs26770(D’=0.533,r2=0.117),nor between rs35941 Linkage equilibrium(D’≠0),rs4311394 has 4 SNP TagSNPs in this study.\.2.The allele and genotype frequencies of the four SNPs of ARL15 gene,rs35941,rs26770,rs4311394,and rs6450176,have achieved genetic balance(P>0.05)in the NGT group,T2DM group,and DN group.3.Comparison of allele frequency and genotype frequency distribution:The allele frequencies and genotype frequencies of the 4 locus in this study have no differences between the Korean and Han ethnicities,because no distinction was made between the Korean and Han ethnicities while conducting tests for the genotype and allele frequency of the 4 locus of ARL 15 gene from all the samples.The results showed that the frequency of TT+CT genotype of rs35941 locus of the ARL 15 gene in the DN group was lower than that in the T2DM group(P=0.026).This appears to have a recessive inheritance characteristic,but no difference was found in allele frequency(P>0.05).4.Results of haplotype analysis:There were 16 haplotypes in the four SNPs of the ARL15 gene,rs35941,rs26770,rs4311394,and rs6450176.In NGT group and T2DM group,Haplotype CTGG has significant difference.(P=0.011,OR=0.194,95%CI:0.048-0.787).In NGT group and DN group,the results of frequency analysis of the haplotypes under random distribution showed that CCGA has significant difference between NGT and DN group(P=0.011,OR=2.159,95%CI:1.181-3.949).In T2DM group and DN group,the results of frequency analysis of the haplotypes under random distribution showed that CCGA has significant difference between T2DM and DN group(P=0.00,OR=3.720,95%CI:2.005-6.902).CTAG also had a significant difference between T2DM group and DN group(P=0.004,OR=1.803,95%CI:1.209-2.688).5.Association analysis of positive combined genotypes with various indicators:Comparing the combined effects of the four SNPs of the ARL15 gene,random combinations were able to form 81 genotype combinations,in this study genotype combinations with frequencies less than 0.03 were not included in statistical analysis,altogether 15 groups of genotypes.(1)The frequency of carrying the CC-CC-AG-AG combined genotype was significantly lower in the T2DM group than in the NGT group(P=0.020,OR=0.111,95%CI:0.031-0.931),suggesting that the CC-CC-AG-AG combination genotype may play a role in protecting NGT from developing T2DM.However,the frequency of carrying the CC-CC-AG-AG combined genotype was significantly greater in the DN group than in the T2DM group(P＝0.005,OR＝18.233,95%CI:2.013-165.159),suggesting that the CC-CC-AG-AG combined genotype is a risk factor for inducing T2DM with DN,and increases the risk of DN in T2DM patients by approximately 18.233 times.(2)The frequency of carrying the CT-CT-AG-AG combined genotype was significantly lower in the DN group than in the NGT group(P=0.030,OR=0.310,95%CI:0.107-0.897),suggesting CT-CT-AG-AG combined genotype may play a role in protecting NGT from DN.6.Correlation analysis between ARL15 and all indicators in the DN group:ARL15 has positive correlation with PA(r value:0.372),which has statistical significance(P=0.014).Conclusion:1.ARL15 gene SNPs rs35941,rs26770,rs4311394,and rs6450176 are susceptible genes for DM and DN among Korean and Han ethnicities in Yanbian region.The dangerous haplotype CCGA can increase the risk of DN from NGT by 2.159 times,DM increases the risk of DN by about 3.720 times,and dangerous haplotype CTAG can increase the risk of DN by 1.803 times.2.Carrying the AG-CC-AG-CC genotype may increase insulin resistance,induce blood lipid disorders,and promote the risk of DN by about 18.233 times,by regulating TG and PA levels.3.In the correlation analysis of biochemical indicators of DN patients,it was found that ARL15 had a positive correlation with PA expression level. |
PDF Full Text Request