Association Of The Vascular Endothelial Growth Factor-2578C/A Polymorphism With Diabetic Retinopathy

Objective: To study the association between vascular endothelial growth factor-2578C/A polymorphism and the risk of diabetic retinopathy. Subjects and Method: Firstly, this Meta analysis aimed to investigate the comprehensive and reliable conclusion in the association of VEGF-2578C/A polymorphism and risk for DR in different races. A systematic search of electronic databases including Pub Med, Cochrane Library, EMbase, VIP, Wanfang technological, CNKI and reference lists of relevant articles was carried out until April, 2014. Case-control studies on the relationship between VEGF-2578C/A SNPs and DR were selected based on inclusion and exclusion criteria, and the relevance of VEGF-2578 C allele to DR, the relevance of VEGF-2578C/A SNPs to DR and the relevance of VEGF-2578 A allele to Caucasian DR were quantitatively analyzed. Begger funnel plot of publication biases on the relationships of VEGF SNPs with the risk of DR under the allele and dominant models was drown. Rev Man 5.0 software was used for the statistical analysis. The pooled odds ratios(ORs) and corresponding 95% confidence intervals(CIs) were used to assess the strength of the association. Secondly, follow the diabetes diagnosis standard of WHO and international diagnose of diabetic retinopathy standards, a total of 213 unrelated patients and healthy people were randomly recruited from The Affiliated Hospital of Luzhou medical college and surrounding counties from May 2014 to Jan 2015, include 79 cases of type 2 diabetic retinopathy(DR), 52 cases of type 2 diabetes mellitus(T2DM) and 82 cases of healthy people(control). 9ml blood was taken from the elbow vein of each subject, 3ml of it was stored at-80°C for latter use, and the other 6ml blood was sent to clinical laboratory for biochemistry and Hb A1 c test. The genomic DNA was extracted for the vascular endothelial growth factor-2578C/A polymorphisms by Polymerase Chain Reaction Restriction Fragment Length Polymorphism analysis(PCR-RFLP). Other clinical characteristics such as Hb A1 c, BMI, TC, TG were measured and recorded at the same time. The date was analysed by SPSS18.0 software. All the VEGF genotype distribution was analysed by Chi-square analysis for test whether followed the Hardy-Weinberg equilibrium. Normally distributed data was demonstrated using means±SD( ± s).Non-normally distributed data was demonstrated using median(quartile range). Measurement data between two groups were compared using t or t’-test, three or more groups of it was compared using variance analysis; Numeration data was compared using Chi-square analysis. Risk factors for type 2 diabetic retinopathy was using multiple logistic regression analysis. Results :(1) A total of 1228 DR cases and 1224 diabetes controls without retinopathy(T2DM and T1DM) were included from 8 independent studies(9 groups of data). A significant relationships between VEGF-2578 A allelic gene and VEGF-2578 AA gene type with DR were found in all samples, and the A allelic gene and AA gene type were the risk genes of DR(A versus C: OR=1.39, 95%CI: 1.08~1.80, Z=2.52, P=0.01, P<0.05; AA versus CC+C/A: OR=1.53, 95% CI: 1.05~2.24, Z=2.20, P=0.03, P<0.05; CC versus AA+C/A: OR=0.70, 95%CI: 0.50~0.98, Z=2.10, P =0.04, P<0.05). When the other two studies which did not meet the Hardy-Weinberg Equilibrium were incorporated in a sensitivity analysis, the results were not materially altered.(2)VEGF-2578 A allelic gene was the risk gene to Europeans with DR(OR=1.50, 95%CI: 1.02~2.21, Z=2.07, P=0.04, P<0.05), but not among Asians in subgroup analysis(AA versus CC+C/A:OR=1.46, 95%CI: 0.72~2.96, Z=1.04, P=0.30, P>0.05; CC versus AA+C/A: OR=0.75, 95%CI: 0.47~1.22, Z =1.16, P=0.25, P>0.05; A versus C: OR=1.29, 95%CI: 0.88~1.91, Z=1.29, P=0.20, P>0.05). No significant publication bias was found.(3)Statistical analysis shows DR and T2 DM group had significant higher Hb A1 c, BMI、TC、TG than control group(P<0.05); VEGF-2578 C allelic gene has significant different between DR and T2 DM group(C versus A: X2=4.74, P=0.03, P<0.05); VEGF-2578 CC gene type maybe the reason for the health people and type 2 diabetes patients develop to the diabetic retinopathy(control: CC versus AA+CA: X2=7.59, P=0.01, P<0.05; T2DM: CC versus AA: X2=4.79, P=0.03, P<0.05; CC versus CA+AA: X2=2.33, P=0.13, P>0.05), and AA type maybe the safe factor for those patients(control: AA versus CC+CA: X2=15.94, P=0.00, P<0.05; T2DM: AA versus CC+CA: X2=4.07, P=0.04, P<0.05).(4)VEGF-2578 C allelic gene is the risk factor of DR, The multiple logistic regression analysis shows OR=1.60, 95%CI: 1.05~2.42, P=0.03, P<0.05.Conclusion:(1) The Meta analysis demonstrates that VEGF-2578C/A is associated with DR, especially in Europeans but not in Asians. VEGF-2578 A allelic gene and AA gene type is the risk factor of DR in Europeans.(2) VEGF-2578C/A is associated with DR in the Chinese Han nationality population, VEGF-2578 C allelic gene is the risk factor for the type 2 diabetes mellitus developing to the diabetic retinopathy, VEGF-2578 CC gene type maybe the risk gene of DR and perhaps AA gene type is the protective gene in the Chinese Han nationality population.