Study On Gene Polymorphism Of Type 2 Diabetes Mellitus Complicated With Retinopathy

Objective:To investigate the relationship between 9 single nucleotide polymorphisms（SNPs）（receptor of advanced glycation end products（AGER）,tumor necrosis factor-α（TNF-α）,osteoprotegerin（OPG）,endothelin-1（EDN1）,vascular endothelial growth factor（VEGF）,interleukin-10（IL-10）complement factor-H（CFH）and micor RNA-146a（mi R-146a））and proliferative diabetic retinopathy in patients with type 2 diabetes mellitus（T2DM）in Guangxi Zhuang Autonomous region.Methods:A total of 700 hospitalized patients with T2DM were included in this case–control study from January 2019 to September 2020.They were divided into two groups:no-diabetic retinopathy（NDR）group（n=386）and proliferative diabetic retinopathy（PDR）group（n=314）.Basic clinical data were collected,and clinical indexes affecting diabetic retinopathy were analyzed.9 tag SNPs（rs1800625 and rs2070600 in AGER,rs1800629 in TNF-α,rs3134069 in OPG,rs5370 in EDN1,rs2010963 in VEGF,rs1800896 in IL-10,rs800292 in CFH and rs2910164 in mi R-146a）were examined using kompetitive allele-specific polymerase chain reaction（KASP）genotyping assays.Welch’s t test and Pearson’s chi-square test were used to analyze whether there were statistical differences in clinical data-related indicators between the groups.The Hardy-Weinberg equilibrium test was used to analyze whether all the SNPs conformed to the Hardy-Weinberg genetic equilibrium law.And the odds ratio（OR）and 95%confidence interval（95%CI）of relative risk were calculated by Binary Logistic Regression.Results:Significant differences were found through the analysis of the systolic blood pressure–whether using insulin or not–and the glomerular filtration rate（GFR）between the two groups(P_{-systolic blood pressure}=0.025,P_-insulin=0.001,P_-GFR=0.013).Logistic regression analysis showed that GFR,systolic blood pressure,and insulin use were all associated with PDR in patients with T2DM(P_-GFR=0.001,OR=1.009,95%CI=1.004-1.014;P_{-systolic blood pressure}=0.002,OR=1.014,95%CI=1.005-1.023;P_-insulin=0.000,OR=2.314,95%CI=1.696-3.158).The genotype frequency distribution of all the 9 SNPs in NDR group and PDR group was in accordance with Hardy-Weinberg equilibrium.Rs1800625 in the AGER gene:there were significant differences in AA and AG genotypes between the groups(x²_-AA=4.584,P_-AA=0.032;x_-²_AG=8.097,P_-AG=0.004).After adjusting for confounding factors,compare with AA genotype and AG+GG genotype in the dominant model,the AG+GG genotype was determined to be associated with an increased risk of PDR(P_{-adjust-value}=0.027,OR=2.227,95%CI=1.095-4.528).Rs2070600 in the AGER gene:there were significant differences among the three genotypes between groups(x²_-TT=4.786,P_-TT=0.029;x²_-TC=9.248,P_-TC=0.002;x²_-CC=15.320,P_-CC=0.001).After adjusting for confounding factors,compare with CC genotype and TT+TC genotype in the dominant model,the TT+TC genotype was determined to be associated with a decreased risk of PDR(P_{-adjust-value}=0.001,OR=0.538,95%CI=0.393-0.735).Rs3134069 in the OPG gene:there were significant differences in AA and AC genotypes between the groups(x²_-AA=14.430,P_-AA=0.001;x²_-AC=13.371,P_-AC=0.001).After adjusting for confounding factors,compare with AA genotype and AC+CC genotype in the dominant model,the AC+CC genotype was determined to be associated with a decreased risk of PDR(P_{-adjust-value}=0.023,OR=0.527,95%CI=0.303-0.914).Rs5370 in the EDN1 gene:there was significant difference in TT genotypes between the groups（x²=4.584,P=0.032）.After adjusting for confounding factors,compare with TT genotype and GG+GT genotype in the recessive model,the TT genotype was determined to be associated with an increased risk of PDR(P_{-adjust-value}=0.011,OR=2.718,95%CI=1.254-5.894).Rs2010963 in the VEGF gene:there were significant differences in GG and CG genotypes between the groups(x²_-GG=7.278,P_-GG=0.007;x²_-CG=8.542,P_-CG=0.003).After adjusting for confounding factors,compare with GG genotype and GC+CC genotype in the dominant model,the GC+CC genotype was determined to be associated with a decreased risk of PDR(P_{-adjust-value}=0.007,OR=0.654,95%CI=0.480-0.891).Rs1800896 in the IL-10gene:there were significant differences in CC,TT and TC genotypes between the groups(x²_-TT=12.987,P_-TT=0.001;x²_-TC=9.958,P_-TC=0.002;x²_-CC=4.977,P_-CC=0.026).After adjusting for confounding factors,compare with TT genotype and CC+TC genotype in the dominant model,the CC+TC genotype was determined to be associated with a increased risk of PDR(P_{-adjust-value}=0.001,OR=2.315,95%CI=1.453-3.689).Rs800292 in the CFH gene:there was significant difference in AA genotype between the groups（x²=4.395,P=0.036）.After adjusting for confounding factors,compare with AA genotype and GA+GG genotype in the recessive model,the AA genotype was determined to be associated with a increased risk of PDR(P_{-adjust-value}=0.044,OR=2.058,95%CI=1.019-4.158).Rs1800629 in the TNF-αgene:there was no significant difference between the groups.Rs2910164 in the mi R-146a gene:there was no significant difference between the groups.Conclusion:Increased systolic blood pressure and decreased GFR may be associated with PDR in patients with T2DM.The rs1800625 and rs2070600 in AGER gene,the rs3134069 in the OPG gene,the rs5370 in the EDN1 gene,the rs2010963 in the VEGF gene,the rs1800896 in the IL-10 gene and the rs800292in the CFH gene are significantly associated with the risk of PDR in Guangxi’s Han population.These SNPs might be the susceptibility loci of PDR in T2DM population.