ObjectiveTo assess the association of vascular endothelial growth factor (VEGF) gene-460C/T and-634C/G polymorphism with diabetic retinopathy (DR) among patients in Asia and European by meta-analysis. MethodsA systematic search of electronic databases (PubMed, Cochrane Library, EMBASE, VIP, Wanfang technological, CNKI, etc.) was carried out until Jun, 2014. Case-control studies on the relationship between genetic polymorphism of VEGF-460C/T and VEGF-634C/G with diabetic retinopathy were included in this analysis. The data were quantitatively analyzed by RevMan 5.0 software after assessing the quality of included studies. The pooled odds ratios (OR) and their corresponding 95% confidence intervals (CI) were used to assess the strength of the association. ResultsVEGF-460C/T (7 studies:899 cases and 786 controls) and VEGF-634C/G (10 studies:1615 cases and 1861 controls) were inclued in this meta-analysis. Significant association was found for-460C/T polymorphism in Aisa (C versus T:OR=1.52, 95%CI was, Z=3.72, P=0.0002; CC versus CT+TT:OR=1.61, 95%CI was[1.22, 1.90], Z=3.05, P=0.002; TT versus CT+CC:OR=0.64, 95%CI was[1.19, 2.19], Z=2.07, P=0.04), and VEGF-634CC gene type was associated with DR in European (OR=1.56, 95%CI[1.08, 2.25], Z=2.37, P=0.02). No significant publication bias was found. ConclusionsThe meta-analysis demonstrated that DR was associated with VEGF-460C/T polymorphism in Asia, and C alleles and CC gene type was the risk polymorphism; VEGF-634C/G polymorphism was not associated with DR, but its CC genotype maybe the risk factor in European. Further case-control studies based on larger sample size are still needed, especially for-634C/G polymorphism.
Objective To measure the concentration of serum transthyretin (TTR) of patients with different stages of diabetic retinopathy (DR). Methods A total of 176 patients with diabetes mellitus were included in this study. There were 104 males and 72 females. The patients aged from 21 to 74 years, with the mean age of (56±11) years. The diabetes duration raged from 1 to 30 years, with the mean diabetes duration of (10±7) years. The HbA1C was 5.2%−14.1%, with the mean HbA1C of (8.6±2.0)%. According to the fundus examination, 58 patients had DR (33.0%), but the other 118 patients not (67.0%). For these DR patients, 10 patients were in stage Ⅰ (5.7%), 26 patients in stage Ⅱ (14.8%), 8 patients in stage Ⅲ (4.5%), and 14 patients in stage Ⅳ (8.0%). The concentration of serum TTR was measured by enzyme-linked immunosorbentassay kit. The differences in the concentration of serum TTR between different DR stages were compared.Bivariate analysis was used to analyze the influencing factors of TTR. Results The concentrations of serum TTR of the patients without DR or with DR of stage Ⅰ to Ⅳ were (224.96±65.47), (383.68±102.99), (247.44±63.21), (228.2±45.89), (189.34±70.12) mg/L, respectively. The difference between different DR stages was statistically significant (F=14.690,P＜0.001).Bivariate analysis showed that the concentration of TTR was correlation to DR (r=0.179,P=0.017). There was no correlation between the concentration of TTR and diabetes duration (r=−0.027,P=0.727), hypertension (r=0.018,P=0.810), hyperlipoidemia (r=0.101,P=0.182), and the use of insulin (r=−0.032,P=0.675). Conclusion The concentration of serum TTR was increased in early DR patients, and gradually decreased with the progression of DR. The concentration of TTR is correlated to DR.
Objective To investigate the effect of intravitreal injection with dexamethasone on leukocyte accumulation, vascular permeability, and the expression of intercellular adhension molecule (ICAM-1) in rats with diabetes. Methods Seventy-two BN rats were divided into 4 groups: control group, diabetes group, diabetes+ physiologic saline group, and diabetes+ dexamethasone group, with 18 rats in each group. Streptozotocin was injected into the rats to set up the diabetic model. Accumulated leukocytes were counted in vivo by acridine orange leukocyte fluorography, and retinal vascular permeability was measured by Evans blue assay. The expression of mRNA and protein level of ICAM-1 were evaluated by real-time quantitative polymerase chain reaction analysis and enzymelinked immunosorbent assay. Results In the diabetes+ dexamethasone group, accumulated leukocytes were reduced, retinal vascular permeability decreased, and the expression of ICAM-1 decreased. The expression of ICAM-1 mRNA and protein levels in control group, diabetes group, diabetes+ physiologic saline group, and diabetes+ dexamethasone group were 0.43plusmn;0.07，0.76plusmn;0.21，0.74plusmn;0.18，and 0.55plusmn;0.13; (37.90plusmn;4.56), (76.74plusmn;6.68), (74.32plusmn;7.11), and (39.61plusmn;4.47) pg/mg respectively. Conclusions Dexamethasone can reduce accumulated leukocytes and retinal vascular permeability, which may be caused by inhibiting the expression of ICAM-1. (Chin J Ocul Fundus Dis,2007,23:273-276)
The pathogenesis of diabetic retinopathy (DR) is more complex. For the upstream of traditional pathogenesis, to looking for unifying mechanism theory which proposed in foundation of common promoters and the latest view of DR may be the result of chronic inflammation. Both of them provide the basic and clinical theraby of DR with new direction. Therefore, there are many related issues still needs to intensive study. （Chin J Ocul Fundus Dis，2008，24：237-239）
Objective To observe the genetic predisposition of complement C5 gene polymorphisms in proliferative diabetic retinopathy (PDR) in Chongqing Han population. Methods 400 type 2 diabetes (T2D) patients (case group) and 600 age- and sex-matched healthy controls (control group) were enrolled in this study. There were 8 PDR patients in case group. All the subjects were Han ethnic people. The immune-related representative SNP locus of C5 gene including rs2269067, rs7040033, rs7027797 were screened by linkage disequilibrium analysis. Locus rs1017119 was selected by TagSNP and was around the above three loci. Subjects′ peripheral venous blood was collected and DNA was extracted. Genotyping was examined by PCR-restriction fragment length polymorphism method. The level of C5 plasma protein was measured by enzyme-linked immunoabsorbent assay. Results The frequency of GG genotype of rs2269067 was significantly increased in PDR patients in cases group compared with controls (Pc=3.4×10-5, OR=1.87, 95%CI=1.43 - 2.44；P=3.1×10-6). There was no differences in frequency of G, CC and CG genotype of rs2269067 between two groups (P=1.4×10-4, 1.000, 1.0×10-6). There were no differences in frequency of G, CC, CG, GG genotype of rs7040033, rs1017119, and rs7027797 between two groups (P > 0.05). The production of C5 plasma protein was significantly increased in case group as compare with control group (P=0.0004). An increased production of C5 plasma protein was observed in rs2269067 GG genotype cases compared to CG or CC cases (P=0.003, 0.001). Conclusion C5 rs2269067 GG genotype may be associated with the PDR of T2D in Chongqing Han population.
It is clear that genetic background contributes to the development and progression of diabetic retinopathy (DR). However, the identification of susceptibility loci through candidate gene approaches, linkage disequilibrium analysis of case-control data and genome wide association study is still in its infancy and faces many challenges due to the complexity of the disease itself. China has rich resources of clinical samples. In order to facilitate elucidating the susceptibility genes of DR in China, we look forward multi-disciplinary, multi-regional collaboration studies integrating novel technologies, such as proteomics, metabolomics and next-generation sequencing to analyze gene-gene and gene-environment interaction factors comprehensively.
Objective To determine the association of -429T/C and G1704T polymorphisms in the receptor for advanced glycation end products gene with proliferative diabetic retinopathy (PDR). Methods Case-control study. From the Beijing Desheng Diabetic Eye Study cohort of 1467 patients with type 2 diabetes mellitus (T2DM),atotal of 97 patients with PDR and 105 diabetic patients without retinopathy (DWR, duration of diabetes 15 years) were included for this study. Questionnaires were collected and general ophthalmologic examinations were performed. Biochemical analysis was conducted. DNA was extracted from peripheral venous blood. The -429T/C and G1704T single nucleotide polymorphisms were detected by the means of PCR-restrication fragment length polymorphisms. Results The frequency distribution of -429T/C in DWR group was 81.0% in TT, 16.1% in TC, 2.9% in CC. The frequency distribution of -429T/C in PDR group was 77.3% in TT, 20.6% in TC, 2.1% in CC. There was no significant statistical difference between the two groups (χ2=0.40, P > 0.05). Frequency of the -429T/C minor alleleCin the DWR and PDR group were 11.0% and 12.4%, respectively, with no significant statistical difference between the two groups (χ2=0.20，P > 0.05). The frequency distribution of G1704T in DWR group was 66.7% in GG, 29.5% in GT, 3.8% in TT. The frequency distribution of G1704T in PDR group was 78.4% in GG, 21.6% in GT. There was no significant statistical difference between the two groups (χ2=3.44, P > 0.05). Frequency of the G1704T minor alleleTin the DWR and PDR group were 18.6% and 10.8%, respectively, in which significant difference was found within the two groups (χ2=4.79, OR=1.88，95%CI: 1.06 - 3.33, P > 0.05). Conclusions G1704T polymorphism is associated with PDR presence and 1704G allele may increase the risk of PDR.