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The Preliminary Study of the Susceptibility Factors of Type2Diabetic Retinopathy in Hunan Province

Author: LiuZuo
Tutor: TangLuoSheng
School: Central South University
Course: Clinical
Keywords: diabetic retinopathy meta-analysis VEGF single nucleotidepolymorphisms VEGFxxx VEGFxxxb susceptibility factors
CLC: R587.2
Type: PhD thesis
Year: 2013
Downloads: 1
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Abstract


Objective:The aim of this study is to discuss genetic and environmental predisposing factors of diabetic retinopathy (DR.) with type2diabetes in Hunan Province and screen the high-risk groups of diabetic retinopathy.(1) To Search VEGF single nucleotide polymorphisms related to diabetic retinopathy in the yellow people by meta-analysis method.(2) To investigate the susceptibility between VEGF single nucleotide polymorphisms and diabetic retinopathy in Hunan Province.(3) To investigate correlation between serum VEGF total protein, isoform VEGF165and VEGF165b with diabetic retinopathy(4)To explore the risk factors of diabetic retinopathy through comparing VEGF single nucleotide polymorphisms, VEGF protein and other demographic characteristics and biochemical parameters by case-control and logistic regression analysis.Methods:(1) Review relevant articles about the VEGF single nucleotide polymorphisms and diabetic retinopathy was carried out until March2012. A systematic search of electronic databases and access to the original literature, development of inclusion and exclusion criteria; and making a meta-analysis by the experimental data.(2) According to the result of meta-analysis, detect VEGF single nucleotide polymorphisms among normal people, diabetic patients with no retinopathy and diabetic retinopathy patients by case-control method in Hunan Province,and do statistical analysis of distribution among the groups by the chi-square test.(3) Enzyme-linked immunosorbent assay was used to detect serum total VEGF、VEGF165and VEGF165b among normal people, diabetic patients with no retinopathy and diabetic retinopathy in Hunan province. Do statistical analysis of distribution among them through group T-test and linear regression analysis and discuss correlation with VEGF single nucleotide polymorphisms and environmental factors.(4) Investigate the susceptibility factors of diabetic retinopathy through a case-control based study among diabetic patients with no retinopathy and diabetic retinopathy on risk factor as demographic characteristics、biochemical parameters、VEGF single nucleotide polymorphisms and VEGF protein expression; Statistical analysis of data by group T-test and logistic regression analysis.Results:(1) Meta-analysis:VEGF rs699947A significant association between it and DR risk was found in dominant model (CA Vs CC)(I2=64%,OR=1.27,95%CI[1.05,1.54],P=0.02),especially in the yellow race(I2=38%,OR=1.46,95%CI[1.17,1.82]p=0.0007).Other models with DR was no significant correlation.(P>0.05).VEGF rs1570360All type of models with DR was no significant correlation.(P>0.05).VEGF rs2010963A significant association between it and DR risk was found in recessive model(CC Vs GC+GG)in the yellow race group by subgroup analysis(I2=60%,OR=1.2895%CI[1.01,1.63],P=0.04);and in recessive model(CC Vs GC+GG)by PCR-RFLR subgroup analysis(I2=46%,OR=1.5095%CI[1.05,2.14],P=0.03)VEGF rs3025039A significant association between it and DR risk was found in co-dominant model (TT Vs CC)(I2=50%,OR=2.47,95%CI[1.11,5.51],P=0.03),especially in the yellow race(I2=51%, OR=3.5395%CI[1.35,9.26],P=0.01).Recessive model(TT Vs CT+CC)with DR was no significant correlation in the white race (P=0.05),but different in the yellow race(I2=33%,OR=3.1995%CI [1.21,8.42],P=0.01).Other models with DR was no significant correlation.(P>0.05).(2)Frequencies of VEGF gene polymorphism genotype and allele between the DWR group and DR group in Hunan province: VEGF rs699947:Frequencies of DR group AA genotype is14.8%, DWR group is4.3%; The CC genotype is48.1%in DR group, DWR group is60.9%(P=0.04,<0.05).The allele A frequency in the DR group is33.3%, and DWR group is21.7%(P=0.016,<0.05). The diabetes patients with rs699947AA genotype occurred the DR risk was3.83times higher than who with CC genotype and CA genotype (OR=3.83).VEGF rs833061:Frequencies of DR group CC genotype is16.0%, DWR group is4.3%; The TT genotype is45.7%in DR group, DWR group is58.7%(P=0.025,<0.05).The allele C frequency in the DR group is35.2%, and DWR group is22.8%(P=0.011,<0.05). The diabetes patients with rs833061CC genotype occurred the DR risk was4.21times higher than who with TTgenotype and TC genotype (OR=4.21).VEGF rs13207351:Frequencies of genotype and allele between the two groups had not statistically significant difference (P>0.05). All rs13207351genotype in patients with diabetes is no significant difference in the risk of DR.VEGF rs2010963:Frequencies of DR group CC genotype is21.0%, DWR group is9.8%; The GG genotype is28.4%in DR group, DWR group is42.4%(P=0.049,<0.05).The allele C frequency in the DR group is46.3%, and DWR group is33.4%(P=0.017,<0.05). The diabetes patients with rs2010963CC genotype occurred the DR risk was2.45times higher than who with GG genotype and GC genotype (OR=2.45).VEGF rs3025039:Frequencies of genotype and allele between the two groups had not statistically significant difference (P>0.05). All rs3025039genotype in patients with diabetes is no significant difference in the risk of DR.(3) VEGF total protein,VEGF165and VEGF165b:1) serum VEGF total protein was44.47±3.42(pg/ml) in normal control group,57.74±11.23(pg/ml) in the DWR group and59.25±11.62(pg/ml) in DR group.Compared with the control group, VEGF total protein in the DWR group and DR group was increased (P<0.05), but the total amount of VEGF between the DWR group and DR group was no statistically significant difference (P>0.05).2) Serum VEGF165was15.89±1.31(pg/ml) in normal control group,22.68±4.52(pg/ml) in the DWR group and27.43±7.29(pg/ml) in DR group.Compared with the control group, VEGF165in the DWR group and DR group was increased (P<0.05).And VEGF165between the DWR group and DR group had statistically significant difference (P=0.025).3) Serum VEGF165b was9.25±0.82(pg/ml) in normal control group,6.97±1.46(pg/ml) in the DWR group and5.43±2.35(pg/ml) in DR group. Content among the three groups showed a gradually decreasing trend, the difference was statistically significant (P<0.05). The ratio of of VEGF165and VEGF165b was changed among the three groups, and the ratio gradually increased (1.72,3.25,5.05).4)The relationship between VEGF protein and VEGF gene: Compared with GG genotype and GA genotype, VEGF protein was significantly higher in the patients with rs2010963CC genotype (62.59±13.71(pg/ml) in the CC genotypes,53.27±10.37(pg/ml) in GA genotype,50.85±10.59(pg/ml) in GG genotype); and the difference had statistically significance (P<0.05).Other SNP genotypes had no statistically significant difference (P>0.05).(4)The susceptibility factors of diabetic retinopathy:1) Systolic blood pressure, diastolic blood pressure, glycosylated hemoglobin and creatinine between the two groups had a statistically significance to analyze demographic characteristics and biochemical parameters between DWR group and DR group by group T-test (P <0.05).2) Logistic regression analysis:diabetic patients with systolic blood pressure over160mmHg had a7.5times higher DR risk than who with130mmHg; diabetic patients with diastolic blood pressure over90mmHg had a2times higher DR risk than who less to90mmHg. Diabetic patients with HbAIC over14.0%had11.50times higher DR risk than with who less to8%. Diabetic patients with Creatinine values above100mmol/L had5.5times higher DR risk than with who less to60mmol/L. Diabetic patients with rs2010963CC genotype had3.2times higher DR risk compared with GG genotype. Diabetic patients with VEGF165above28.0mmol/L had9.3times higher DR risk than with who less to28.0mmol/L. Diabetic patients with VEGF165b above5.0mmol/L had lower DR risk than with who less to5.0mmol/L (OR=0.013).VEGFi65b has a significant protective effect for people with diabetes.5. Conclusions:(1) The co-dominant model (CA Vs CC) of VEGF rs699947, the implicit model (CC Vs GC+GG) of VEGF rs2010963, the co-dominant model (TT Vs CT+CC) and the implicit model (TT Vs CC) of VEGF rs3025039, are associated with the occurrence of diabetic retinopathy in the yellow race, but have no obvious correlation diabetic retinopathy in the white race.(2) The polymorphism variation of rs699947, rs833061and rs2010963of the VEGF gene has significance in the occurrence and development of diabetic retinopathy in the population of Hunan province.(3) The change of the ratio of VEGFxxx and VEGFxxxb leads to the initiation and progression of diabetic retinopathy. The polymorphism variation of rs2010963is a functional change, which is important for occurrence of diabetic retinopathy in diabetic patients.(4) People with SBP≥160mmHg, DBP≥90mmHg, glycosylated hemoglobin≥8.0mmol/L, Creatinine values≥100mmol/L,28mmol/L, rs2010963CC gene and VEGF165b<5.0mmol/L have high risk for diabetic retinopathy.

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CLC: > Medicine, health > Internal Medicine > Endocrine diseases and metabolic diseases > Islet disease > Diabetic coma and other complications
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