The Association Between VEGF-1190G/A Polymorphism And Diabetic Retinopathy In Type 2 Diabetes

Background and objective: Diabetic retinopathy (DR) is one of the most common and severe microvascular complications of diabetes mellitus (DM), and it has become one of the four main diseases in the world which can lead to be blind. The pericapillary cells disappearance, blood-retinal barrier (BRB) breakdown and retinal neovascularization are the basic pathological changes of DR. The pathogenesy of DR is not elucidated completely now. Some research has indicated that the combination of multiple factors and ways can lead to DR. The duration of diabetes mellitus and fasting blood glucose control are closely associated with the development of DR. Most diabetic patients, especially those who have long duration of diabetes mellitus and poorly blood glucose control are susceptible to DR. But the duration and blood glucose control are not completely associated with the development of DR. A study showed that about 28.8% of diabetic patients develop DR early, but still about 22.2% of diabetic patients irrespective of the level of blood glucose do not develop DR. This study revealed that genetic factors may be the initiating agent. For the past few years, as the rapid development of molecular biology, scholars in and out China have screened the possible candidate genes of DR by researching, and have been analyzing the effects of the genetic factors on DR from polymorphism and gene regulation. VEGF gene is one of the numerous candidate genes. Although the studies about the association of DR with its candidate genes have made some progress, but there are still no definite conclusions presently.Vascular endothelial growth factor (VEGF) also called vascular permeability factor can specially bind with vascular endothelial cells and make its biology effects. It can increase the permeability of microvasculature and stimulate neovascularization. VEGF plays an important role in the development of DR. The single nucleotide polymorphism (SNP) of VEGF gene may influence its transcription or translation, thus it may be associated with many kinds of diseases. There are many studies on the relationship between VEGF gene polymorphism and the genetic susceptibility of DR, but the results are not identical. So it is necessary to make deeply studies. There are many SNPs in the promoter region, 5'and 3'untranslate region of VEGF gene. The -1190G/A polymorphism is in the promoter region of VEGF gene. It may influence the expression level of the gene and indue the development of DR. The aim of this study is to investigate the association between the -1190G/A polymorphism in promoter region and DR in the Chinese Han people coming from Shijiazhuang by using polymerase chain reaction-ligase detection reaction (PCR-LDR).Methods: This study adopted case-cotrol research method. 324 patients with type 2 diabetes mellitus (T2DM) were enrolled randomly. Among them, there were 124 patients with non-proliferative diabetic retinopathy (NPDR), 56 subjects with proliferative diabetic retinopathy (PDR), and 144 individuals without DR as controls. All the subjects were the the Chinese Han people coming from Shijiazhuang and there was no blood relationship among them. For DNA isolation,5ml venous blood sample from each subject was collected. The DNA was extracted from peripheral blood leukocytes by proteinase K digestion and salting out procedure. The genotypes and alleles of the -1190G/A were analyzed by PCR-LDR. Statistical analysis was performed by using SPSS13.0 software package. The level of significance adopted was P<α=0.05 was considered significant. All the measurement data was tested the normality. Normally distributed data was demonstrated by means±SD and non-normally distributed data by median (inter-quartile range). The genotypes were analyzed by Chi-square test to test whether the genotype distribution followed the Hardy-Weinberg equilibrium. The measurement data was compared by t test, and the enumeration data was compared by Chi-square test. Non-conditional Logistic regression was performed to calculate the odds ratio(OR) and 95% confidence interval(CI). Results:1 The systolic and diastolic pressure of the patients with NPDR was higher than controls (p<0.05). The fasting blood glucose, systolic pressure, diastolic pressure and duration of diabetes mellitus of the patients with PDR was higher than controls (P<0.05). The patients with PDR had higher level of fasting blood glucose and suffered with diabetes longer than with controls (OR95%CI=2.306(1.150-4.625),2.221(1.439-3.427)).2 The genotype frequencies of VEGF in control, NPDR and PDR group were followed the Hardy-Weinberg equilibrium(P>0.05).3 The comparison of allele and genotype frequencies of the three groups: There was statistical significance of allele frequency between NPDR group and control group(χ~2=8.213,P=0.004<0.05),and the OR95%CI of the G allele was 1.834(1.207-2.785).There was no statistical significance of allele frequency between PDR group and control group(χ~2=0.145,P=0.704>0.05),and the OR95%CI of the G allele was 1.101(0.671-1.086). NPDR group compared with control group, there was statistical significance of genotype frequency distribution(χ~2=7.786,P=0.020<0.05),and the OR 95%CI of the GG genotype against the AA+AG genotype adjusted by blood glucose, blood pressure and duration of DM was 1.950(1.155-3.293). PDR group compared with control group, there was no statistical significance of genotype frequency distribution(χ~2=0.134,P=0.935>0.05),and the OR 95%CI of the GG genotype against the AA+AG genotype adjusted by blood glucose, blood pressure and duration of DM was 1.225(0.615-2.440).Conclusions:1 Among the Chinese Han people who come from Shijiazhuang and suffered with T2DM, the fasting blood glucose control and duration of diabetes mellitus were positively associated with the risk of PDR.2 VEGF-1190G/A gene polymorphism was associated with NPDR, and the -1190G allele was probably a susceptible gene of NPDR.