Study The Relationship Of Clinical Index And Gene Polymorphisms With The Diabetic Retinopathy

ObjectiveDiabetic retinopathy(DR) is one of the most common microvascular complications of diabetes. Clinical factors, such as duration of diabetes blood glucose levels, blood pressure, blood lipids, have a certain influence on the development of diabetic retinopathy. However, diabetic retinopathy patients have great individual differences in the incidence of disease duration and severity, this difference is considered to differences in patient-derived polymorphism associated genes. The purpose of this study from two aspects of clinical indicators and gene polymorphism to analysis related factors,which affected the occurs and development of diabetic retinopathy.Materials and methodsSince June 1, 2014 to June 31, 2015, with reference to the relevant diagnostic criteria and exclusion criteria, we collected 319 cases of diabetic patients in Inner Mongolia Hospital of Endocrinology, while collecting 387 controls in the same period of comparison. According to fundus fluorescein angiography were divided into non-diabetic retinopathy(NDR group) and diabetic retinopathy(DR group), wherein the DR group were 175 and NDR group 144. Record the fasting blood glucose, glycosylated hemoglobin, total cholesterol, triglycerides, LDL, HDL, urea, creatinine, cystatin C and other indicators, as well as inquire the duration of diabetes, hypoglycemic agents and insulin usage.All continuous data are presented as means±standard deviations(SDs). Pearson’s x2 test and T-test were used to compare the distribution of categorical variables and continuous variables, respectively. Differences in continuous variables among the subjects with three genotypes of related genes were assessed using the ANOVA. Each SNP frequency in control subjects was tested for departure from Hardy–Weinberg Equilibrium(HWE). We calculated the genotype frequencies of case and control subjects using the chi square test. Odds ratio(OR) and 95% confidence intervals(CIs) were calculated by unconditional logistic regression.Statistical analyses were performed using Microsoft Excel, SPSS 19.0 statistical package(SPSS, Chicago, IL), Haploview and SNPstats software. And two-sided p < 0.05 were considered statistically significant.ResultsPearson’s chi-square test analysis found that the frequency distribution of insulin therapy in patients between DR and NDR group was significantly different; Welch’s t-test analysis found that the mean of age, duration of diabetes, Total cholesterol, Triglycerides, LDL, GFR, CP in DR and NDR was significant difference between DR and NDR group.We used the ANOVA method to analyze the relationship between the SNP and clinical indicators of diabetes mellitus and diabetic retinopathy. We found that the mean of Hb A1 c exist significant differences in KIAA0825 rs17376456 and IGF1 rs6214 loci different genotypes. The mean of TG exist significant differences in LEKR1-CCNL1 rs13064954 and ARHGAP22 rs4838605 loci different genotypes.In the analysis results of diabetic retinopathy, we found that MTHFR rs1537516 loci affect triglyceride mean in different genotypes, the mean in the AG genotype was significantly higher than wild type. Also found MTHFR rs1537516 affect insulin levels in diabetic retinopathy patients. We also found that the mean of Cys-c exist significant differences in different genotypes of ULEKR1-CCNL1 rs13064954 site and NOS3 rs3918227 sites.We analyzed the association between the gene polymorphisms and diabetes mellitus and diabetic retinopathy. We found that LEKR1-CCNL1 rs13064954(G>A) decreased the risk of diabetic retinopathy(OR = 0.57, 95%CI: 0.34-0.96, p = 0.032).We analyzed all of the SNPs using genetic models with unconditional logistic regression adjusted for age and gender. We found that IGSF21-KLHDC7 A rs3007729(C>T) increased the risk of diabetes mellitus under the Log-additive model(OR = 1.26, 95%CI: 1.01-1.56, p = 0.037). Under the co-dominant model, rs1799983 GT genotype and rs3918227 CA genotype in NOS3 gene and ARHGAP22 rs4838605 TC genotype can actually increase the risk of diabetes mellitus(rs1799983: OR = 1.49, 95%CI : 1.02-2.18, p = 0.002; rs3918227: OR = 1.41, 95%CI : 0.91-2.20, p = 0.046; rs4838605: OR = 1.54, 95%CI : 1.06-2.24, p = 0.003).We analyzed all of the SNPs using genetic models with unconditional logistic regression. We found that IGSF21-KLHDC7 A rs3007729 TT genotype can increased the risk of diabetic retinopathy in the co-dominant model(OR = 2.11, 95%CI: 1.26-3.53, p = 0.013). We also found that LEKR1-CCNL1 rs13064954(G>A) decreased the risk of diabetic retinopathy(OR = 0.58, 95%CI: 0.34-0.96, p = 0.034).ConclusionNOS3 rs1799983 and rs3918227 and ARHGAP22 rs4838605 polymorphism was significantly associated with diabetes mellitus;LEKR1-CCNL1 rs13064954 polymorphism was significantly associated with diabetic retinopathy;IGSF21-KLHDC7 A rs3007729 gene polymorphism was significantly associated with diabetes mellitus and diabetic retinopathy;KIAA0825 rs17376456 and IGF1 rs6214 polymorphism was significantly associated with Hb A1 c in the diabetes mellitus patients.LEKR1-CCNL1 rs13064954 and ARHGAP22 rs4838605 polymorphism was significantly associated with TG level in the diabetes mellitus patients.MTHFR rs1537516 locus was significantly associated with triglycerides and insulin levels in the diabetic retinopathy patients.