湖南地区2型糖尿病视网膜病变易感性因素初步研究
发布时间：2018-08-20 17:56
【摘要】：目的： 研究湖南地区2型糖尿病视网膜病变(diatetic retinopathy,DR)遗传及环境易感因素；筛选糖尿病视网膜病变发生的高危人群。 (1)采用荟萃分析方法,搜寻黄种人中与糖尿病视网膜病变发生相关的血管内皮生长因子(vascular endothelial growthfactor,VEGF)单核苷酸多态性位点。 (2)探讨湖南地区人群中VEGF单核苷酸多态性位点与糖尿病视网膜病变易感性的关联性。 (3)探讨血清中VEGF蛋白总量,亚型VEGF165及其异构体VEGF165b含量与糖尿病视网膜病变的相关性。 (4)采用病例对照及logistic回归分析比较VEGF单核苷酸多态性位点、VEGF蛋白及其他人口学特征和生化指标,探讨糖尿病视网膜病变发生的高危因素。 方法： (1)回顾2012年3月前有关VEGF单核苷酸多态性与糖尿病视网膜病变的所有英文文献。系统性检索及获取原始文献、制定纳入及排除标准；将单核苷酸多态性位点与糖尿病视网膜病变相关的实验数据进行荟萃分析。 (2)根据荟萃分析显示黄种人中有意义的VEGF单核苷酸多态性位点,采用病例对照方法,使用限制性片段长度多态性聚合酶链反应(PCR-RFLR)检测其在湖南地区正常人、糖尿病无视网膜病变患者(diabetic without retinopathy, DWR)、鐕糖尿病视网膜病变患者(diabetic retinopathy, DR)的分布,通过卡方检验统计分析其在各组间的分布差异。 (3)采用病例对照方式,使用酶联免疫吸附测定法检测湖南地区正常人,糖尿病无视网膜病变患者,糖尿病视网膜病变患者的血清中VEGF总量,亚型/EGF165及其异构体VEGF165b含量,通过成组T检验及线性回归分析统计分析其含量在各组间的分布差异,及与、/EGF单核苷酸多态性位点及环境因素间的关联性。 (4)采用病例对照方式,统计糖尿病无视网膜病变患者,糖尿病视网膜病变患者的人口学特征及生化指标的相关数据及VEGF单核苷酸多态性位点及VEGF蛋白表达,进行成组T检验及logistic回归分析,探讨糖尿病视网膜病发生的高危易感因素。 结果： (1)荟萃分析结果： VEGF rs699947共显性模型-杂合型／野生型(CAVs CC)与DR发病风险存在相关性(I2=64%, OR=1.2795%CI [1.05,1.54], P=0.02),尤其在黄色人种中(I2=38%, OR=1.4695%CI [1.17,1.82], P=0.0007)。其它模型与DR发病无显著相关性(P0.05) VEGF rs1570360各模型在各色人种中与DR的发病无显著相关性(P0.05)。 VEGF rs2010963亚组分析：黄色人种组隐性模型(CC V s GC+GG)显示与DR的发病相关(I2=60%, OR=1.2895%CI [1.01,1.63], P=0.04); PCR-RFLR测序方式组隐性模型(CC V s GC+GG)与DR的发生明显相关(I2=46%, OR=1.5095%CI [1.05,2.14], P=0.03) VEGF rs3025039共显性模型-纯和型／野生型(TT Vs CC)与DR发病风险存在相关性(I2=50%, OR=2.4795%CI [1.11,5.51], P=0.03),特别是在黄色人种中(I2=51%, OR=3.5395%CI [1.35,9.26], P=0.01)。隐性模型(TT Vs CT+CC)白色人种与DR发病无明显相关性(P=0.05),在黄色人种中示与DR的发生相关(I2=33%, OR=3.1995%CI [1.21,8.42], P=0.01);其它各模型与DR的发病无明显相关性(P0.05)。 (2)本省人群中DWR组与DR组VEGF基因多态性位点基因型频率及等位基因频率： VEGF基因rs699947位点：DR组AA基因型分布频率为14.8%,DWR组为4.3%；CC基因型DR组为48.1%,DWR组为60.9%(P=0.04,0.05),其等位基因A频率在DR组为33.3%,DWR组为21.7%(P=0.016,0.05)。携带rs699947AA基因型的糖尿病患者发生DR的危险性较rs699947CC基因型及CA基因型携带者高3.83倍(OR=3.83)。 VEGF基因rs833061位点：DR组CC基因型分布频率为16.0%,DWR组为4.3%；TT基因型DR组为45.7%,DWR组为58.7%(P=0.025,0.05),其等位基因C频率在DR组为35.2%,DWR组为22.8%(P=0.011,0.05)。携带rs833061CC基因型的糖尿病患者发生DR的危险性较rs833061TT基因型及TC基因型携带者高4.21倍(OR=4.21)。 VEGF基因rs13207351位点：基因型频率及等位基因频率在研究组和对照组间的差异无明显统计学意义(P0.05)。携带rs13207351GG基因型、GA基因型及AA基因型的糖尿病患者发生DR的危险性没有明显差别。 VEGF基因rs2010963位点：DR组CC基因型分布频率为21.0%,DWR组为9.8%。GG基因型DR组为28.4%,DWR组为42.4%(P=0.049,0.05),其等位基因C频率在DR组为46.3%,DWR组为33.4%(P=0.017,0.05)。携带rs2010963CC基因型的糖尿病患者发生DR的危险性较rs2010963GG基因型及GC基因型携带者高2.45倍(OR=2.45)。 VEGF基因rs3025039位点：基因型频率及等位基因频率在研究组和对照组间的差异无明显统计学意义(P0.05)。携带rs3025039CC基因型、CT基因型及TT基因型的糖尿病患者发生DR的概率没有明显统计差异。 (3) VEGF蛋白总量、VEGF165含量和VEGF165b含量： 1)正常对照组中血清VEGF总量为44.47±3.42(pg/ml), DWR组血清VEGF总量为57.74±11.23(pg/ml), DR组59.25±11.62(pg/ml),DWR组及DR组的VEGF总量都较正常对照组升高(P0.05),但DWR组与DR组之间VEGF总量没有明显的统计学差异(P0.05)。 2)正常对照组中VEGF165含量为15.89±1.31(pg/ml), DWR组为22.68±4.52(pg/ml); DR组为27.43±7.29(pg/ml),与正常对照组比具有统计学意义(P0.05)；且VEGF165在D WR组及DR组之间也有显著差异(P=0.025)。 3)VEGF165b在血中的含量在正常对照组为9.25±0.82(pg/ml); DWR组为6.97±1.46(pg/ml); DR组为5.43±2.35(pg/ml).其含量在三组之间呈现逐渐降低的趋势,差异具有统计学意义(P0.05)。VEGF165及VEGF165b的比值在三组间出现变化,比值逐渐增大(1.72、3.25、5.05)。 4)蛋白总量与基因位点：携带rs2010963CC基因型人群其血中VEGF蛋白含量较GG基因型及GA型显著增高(CC基因型VEGF蛋白含量为62.59±13.71(pg/ml),GA基因型蛋白含量为53.27±10.37(pg/ml),GG基因型蛋白含量为50.85±10.59(pg/ml));CC基因型与GG基因型及GC基因型比较均具有统计学上的显著性差异,P0.05),其他各SNP位点各基因型之间无明显统计学差别(P0.05)。 (4)糖尿病视网膜病变易感因素分析： 1)DWR组及DR组之间的人口学特征及生化指标的相关数据进行成组T检验,发现收缩压、舒张压、糖化血红蛋白及肌酐值在两组之间存在显著的统计学差异(P0.05)。 2)logistic回归分析：收缩压高于160mmHg的糖尿病患者发生DR的危险性较低于130mmHg的高7.5倍,舒张压高于90mmHg的糖尿病患者发生DR的危险性较低于90mmHg的高2倍。HbAIC含量高于14.0%的糖尿病患者发生DR的危险性较低于8.0%的高11.50倍。肌酐值高于100mmol/L的糖尿病患者发生DR的危险性较低于60mmol/L的高出5.5倍。携带rs2010963CC基因型糖尿病患者发生DR的危险性较GG基因型患者高3.2倍。VEGF165含量高于28.0mmol/L的糖尿病患者发生DR的危险性较低于28.0mmol/L的患者高9.3倍,而VEGF165b含量高于5.0mmol/L的糖尿病患者发生DR的危险性较低于5.0mmol/L的患者明显降低(OR=0.013),VEGF165b对于糖尿病患者有明显保护作用。 结论： (1)黄色人种中VEGF rs699947的共显性模型(C A Vs C C)、 VEGF rs2010963隐性模型(CC Vs GC+GG)及VEGF rs3025039的共显性模型(TT Vs CC)、隐性模型(TT Vs CT+CC)跟糖尿病视网膜病变的发生相关；而在白色人种中上述多态性位点与糖尿病视网膜病变无明显相关性。 (2)本省人群VEGF基因rs699947位点、VEGF基因rs833061位点、VEGF基因rs2010963位点的多态性变化在糖尿病视网膜病变发生发展中具有一定的意义 (3)VEGFXXX与EGFxxxb比值改变导致糖尿病视网膜病变的发生和发展。rs2010963位点多态性变化为功能性改变,对糖尿病患者发生糖尿病视网膜病变有重要意义。 (4)收缩压≥160mmHg舒张压≥90mmHg.糖化血红蛋白≥8.0mmol/L、肌酐值≥VEGF16528mmol/L、rs2010963CC基因型及VEGF165b5.0mmol/L为糖尿病视网膜病变发生的高危人群。
[Abstract]:Objective:
Objective To study the genetic and environmental susceptibility factors of type 2 diabetic retinopathy (DR) in Hunan province, and to screen the high risk population for DR.
(1) Single nucleotide polymorphisms of vascular endothelial growth factor (VEGF) associated with diabetic retinopathy in yellow race were searched by meta-analysis.
(2) To explore the association between single nucleotide polymorphism of vascular endothelial growth factor (VEGF) and susceptibility to diabetic retinopathy in Hunan population.
(3) To investigate the correlation between serum total VEGF protein, subtype VEGF 165 and its isomer VEGF 165b and diabetic retinopathy.
(4) Case-control and logistic regression analysis were used to compare the single nucleotide polymorphisms of vascular endothelial growth factor (VEGF), the protein of vascular endothelial growth factor (VEGF) and other demographic and biochemical characteristics, and to explore the risk factors of diabetic retinopathy.
Method:
(1) To review all the English literature on the relationship between single nucleotide polymorphism of vascular endothelial growth factor and diabetic retinopathy before March 2012.
(2) According to meta-analysis, the significant single nucleotide polymorphisms of vascular endothelial growth factor (VEGF) in yellow race were detected by restriction fragment length polymorphism polymerase chain reaction (PCR-RFLR) in Hunan, diabetic without retinopathy (DWR), diabetic retinopathy (DR) and diabetic retinopathy (DR). The distribution of diabetic retinopathy (DR) was analyzed by chi-square test.
(3) Serum levels of VEGF, subtype/EGF165 and its isomer, VEGF 165b, were measured by enzyme-linked immunosorbent assay (ELISA) in Hunan normal subjects, diabetic patients without retinopathy and diabetic patients with retinopathy. The correlation between /EGF and single nucleotide polymorphisms and environmental factors.
(4) The demographic characteristics and biochemical data of diabetic retinopathy patients without retinopathy and diabetic retinopathy patients with diabetic retinopathy and the expression of VEGF single nucleotide polymorphism site and VEGF protein were analyzed by case-control method. T-test and logistic regression were used to explore the risk factors of diabetic retinopathy.
Result:
(1) meta analysis results:
Vascular growth factor rs699947 co-dominant model-heterozygous/wild type (CAVs CC) was associated with DR risk (I 2 = 64%, OR = 1.2795% CI [1.05, 1.54], P = 0.02), especially in yellow people (I 2 = 38%, OR = 1.4695% CI [1.17, 1.82], P = 0.0007). Other models had no significant correlation with DR risk (P 0.05).
There was no significant correlation between the VEGF rs1570360 models and the incidence of DR in all races (P0.05).
Subgroup analysis of VEGF rs2010963: Recessive model of yellow race group (CC V s GC+GG) showed a significant association with DR (I 2 = 60%, OR = 1.2895% CI [1.01, 1.63], P = 0.04); recessive model of PCR-RFLR sequencing group (CC V s GC+GG) was significantly associated with DR (I 2 = 46%, OR = 1.5095% CI [1.05, 2.14], P = 0.03)
The co-dominant model of VEGF rs3025039-pure and wild type (TT Vs CC) was correlated with the risk of DR (I 2 = 50%, OR = 2.4795% CI [1.11, 5.51], P = 0.03), especially in yellow races (I 2 = 51%, OR = 3.5395% CI [1.35, 9.26], P = 0.01). The recessive model (TT Vs CT + CC) had no significant correlation with DR (P = 0.05) in white races and yellow races (P = 0.05). It was found that DR was associated with DR (I 2 = 33%, OR = 3.1995% CI [1.21, 8.42], P = 0.01); other models had no significant correlation with DR (P 0.05).
(2) genotype frequencies and allele frequencies of VEGF gene polymorphisms in DWR and DR groups in this province:
The distribution frequency of vascular endothelial growth factor gene rs699947 was 14.8% in DR group and 4.3% in DWR group, 48.1% in CC genotype DR group, 60.9% in DWR group (P = 0.04, 0.05). The allele A frequency was 33.3% in DR group and 21.7% in DWR group (P = 0.016, 0.05). The risk of DR in diabetic patients with rs699947AA genotype was higher than that of rs699947CC genotype and CA gene. The carriers were 3.83 times higher (OR=3.83).
The distribution frequency of vascular endothelial growth factor gene rs833061 was 16.0% in DR group and 4.3% in DWR group, 45.7% in TT genotype DR group and 58.7% in DWR group (P = 0.025, 0.05). The allele C frequency was 35.2% in DR group and 22.8% in DWR group (P = 0.011, 0.05). The risk of DR in diabetic patients with rs833061CC genotype was higher than that of rs833061TT genotype and TC gene. The carriers were 4.21 times higher (OR=4.21).
There was no significant difference in genotype frequency and allele frequency between the study group and the control group (P 0.05). There was no significant difference in the risk of DR between diabetic patients with rs13207351GG genotype, GA genotype and AA genotype.
The distribution frequency of CC genotype was 21.0% in DR group and 9.8% in DWR group, 28.4% in GG genotype DR group, 42.4% in DWR group (P = 0.049, 0.05), and 46.3% in DR group and 33.4% in DWR group. The carriers were 2.45 times higher (OR=2.45).
There was no significant difference in genotype frequency and allele frequency between the study group and the control group (P 0.05). There was no significant difference in the incidence of DR among diabetic patients with rs3025039CC genotype, CT genotype and TT genotype.
(3) total VEGF protein, VEGF165 content and VEGF165b content:
1) The total level of serum VEGF in normal control group was 44.47 (+ 3.42) (pg / ml), 57.74 (+ 11.23) (pg / ml) in DWR group, 59.25 (+ 11.62) (pg / ml) in DR group, and increased in DWR group and DR group compared with normal control group (P 0.05), but there was no significant difference between DWR group and DR group (P 0.05).
2) The content of VEGF 165 in normal control group was 15.89 (+ 1.31) (pg/ml), 22.68 (+ 4.52) (pg/ml) in DWR group, 27.43 (+ 7.29) (pg/ml) in DR group, and there was significant difference between DWR group and DR group (P = 0.025).
3) The levels of VEGF 165b in blood were 9.25 (+ 0.82) (pg/ml) in the normal control group, 6.97 (+ 1.46) (pg/ml) in the DWR group, and 5.43 (+ 2.35) (pg/ml) in the DR group. The levels of VEGF 165b decreased gradually among the three groups, and the difference was statistically significant (P 0.05). The ratios of VEGF 165 and VEGF 165b changed among the three groups, and gradually increased (1.72, 3.25, 5.05).
4) Total protein and gene locus: The content of VEGF protein in serum of the population with rs2010963CC genotype was significantly higher than that of GG genotype and GA genotype (the content of VEGF protein in CC genotype was 62.59 [13.71], that of GA genotype was 53.27 [10.37], and that of GG genotype was 50.85 [10.59], that of CC genotype and GG genotype and GC genotype were significantly higher than that of the population with rs2010963CC genotype and GA genotype. Genotype comparison showed significant difference (P 0.05), and there was no significant difference among other SNP loci (P 0.05).
(4) predisposing factors of diabetic retinopathy:
1) The data of demographic characteristics and biochemical indexes between DWR group and DR group were tested by T-test in groups. The results showed that there were significant differences in systolic blood pressure, diastolic blood pressure, glycosylated hemoglobin and creatinine between the two groups (P 0.05).
2) Logistic regression analysis: diabetic patients with systolic blood pressure higher than 160 mmHg had a 7.5-fold lower risk of DR than 130 mmHg, diabetic patients with diastolic blood pressure higher than 90 mmHg had a 2-fold higher risk of DR than 90 mmHg, diabetic patients with HbAIC content higher than 14.0% had a 11.50-fold higher risk of DR than 8.0% and high creatinine value. The risk of DR was 5.5 times lower in diabetics with 100 mmol/L than in patients with 60 mmol/L. The risk of DR was 3.2 times higher in diabetics with rs2010963CC gene than in patients with GG genotype. The risk of DR in 5.0 mmol/L diabetic patients was significantly lower than that in 5.0 mmol/L diabetic patients (OR = 0.013). VEGF 165b has a protective effect on diabetic patients.
Conclusion:
(1) The co-dominant model (C A Vs C), recessive model (CC Vs GC+GG) and co-dominant model (TT Vs CC) of VEGF rs699947 and recessive model (TT Vs CT+CC) of VEGF rs3025039 were associated with diabetic retinopathy in yellow people, but the above polymorphisms were not associated with diabetic retinopathy in white people. Customs.
(2) The polymorphism of rs699947, rs833061 and rs2010963 of vascular endothelial growth factor gene may play an important role in the development of diabetic retinopathy.
(3) The change of the ratio of VEGF XXX to EGF xxxb leads to the occurrence and development of diabetic retinopathy. The change of rs2010963 polymorphism is a functional change, which is important for diabetic retinopathy.
(4) Systolic blood pressure (> 160mmHg) diastolic blood pressure (> 90mmHg), glycosylated hemoglobin (> 8.0mmol/L), creatinine (> VEGF 16528mmol/L), rs2010963CC genotype and VEGF 165b5.0mmol/L are high risk groups for diabetic retinopathy.
【学位授予单位】：中南大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R587.2;R774.1
本文编号：2194513
[Abstract]:Objective:
Objective To study the genetic and environmental susceptibility factors of type 2 diabetic retinopathy (DR) in Hunan province, and to screen the high risk population for DR.
(1) Single nucleotide polymorphisms of vascular endothelial growth factor (VEGF) associated with diabetic retinopathy in yellow race were searched by meta-analysis.
(2) To explore the association between single nucleotide polymorphism of vascular endothelial growth factor (VEGF) and susceptibility to diabetic retinopathy in Hunan population.
(3) To investigate the correlation between serum total VEGF protein, subtype VEGF 165 and its isomer VEGF 165b and diabetic retinopathy.
(4) Case-control and logistic regression analysis were used to compare the single nucleotide polymorphisms of vascular endothelial growth factor (VEGF), the protein of vascular endothelial growth factor (VEGF) and other demographic and biochemical characteristics, and to explore the risk factors of diabetic retinopathy.
Method:
(1) To review all the English literature on the relationship between single nucleotide polymorphism of vascular endothelial growth factor and diabetic retinopathy before March 2012.
(2) According to meta-analysis, the significant single nucleotide polymorphisms of vascular endothelial growth factor (VEGF) in yellow race were detected by restriction fragment length polymorphism polymerase chain reaction (PCR-RFLR) in Hunan, diabetic without retinopathy (DWR), diabetic retinopathy (DR) and diabetic retinopathy (DR). The distribution of diabetic retinopathy (DR) was analyzed by chi-square test.
(3) Serum levels of VEGF, subtype/EGF165 and its isomer, VEGF 165b, were measured by enzyme-linked immunosorbent assay (ELISA) in Hunan normal subjects, diabetic patients without retinopathy and diabetic patients with retinopathy. The correlation between /EGF and single nucleotide polymorphisms and environmental factors.
(4) The demographic characteristics and biochemical data of diabetic retinopathy patients without retinopathy and diabetic retinopathy patients with diabetic retinopathy and the expression of VEGF single nucleotide polymorphism site and VEGF protein were analyzed by case-control method. T-test and logistic regression were used to explore the risk factors of diabetic retinopathy.
Result:
(1) meta analysis results:
Vascular growth factor rs699947 co-dominant model-heterozygous/wild type (CAVs CC) was associated with DR risk (I 2 = 64%, OR = 1.2795% CI [1.05, 1.54], P = 0.02), especially in yellow people (I 2 = 38%, OR = 1.4695% CI [1.17, 1.82], P = 0.0007). Other models had no significant correlation with DR risk (P 0.05).
There was no significant correlation between the VEGF rs1570360 models and the incidence of DR in all races (P0.05).
Subgroup analysis of VEGF rs2010963: Recessive model of yellow race group (CC V s GC+GG) showed a significant association with DR (I 2 = 60%, OR = 1.2895% CI [1.01, 1.63], P = 0.04); recessive model of PCR-RFLR sequencing group (CC V s GC+GG) was significantly associated with DR (I 2 = 46%, OR = 1.5095% CI [1.05, 2.14], P = 0.03)
The co-dominant model of VEGF rs3025039-pure and wild type (TT Vs CC) was correlated with the risk of DR (I 2 = 50%, OR = 2.4795% CI [1.11, 5.51], P = 0.03), especially in yellow races (I 2 = 51%, OR = 3.5395% CI [1.35, 9.26], P = 0.01). The recessive model (TT Vs CT + CC) had no significant correlation with DR (P = 0.05) in white races and yellow races (P = 0.05). It was found that DR was associated with DR (I 2 = 33%, OR = 3.1995% CI [1.21, 8.42], P = 0.01); other models had no significant correlation with DR (P 0.05).
(2) genotype frequencies and allele frequencies of VEGF gene polymorphisms in DWR and DR groups in this province:
The distribution frequency of vascular endothelial growth factor gene rs699947 was 14.8% in DR group and 4.3% in DWR group, 48.1% in CC genotype DR group, 60.9% in DWR group (P = 0.04, 0.05). The allele A frequency was 33.3% in DR group and 21.7% in DWR group (P = 0.016, 0.05). The risk of DR in diabetic patients with rs699947AA genotype was higher than that of rs699947CC genotype and CA gene. The carriers were 3.83 times higher (OR=3.83).
The distribution frequency of vascular endothelial growth factor gene rs833061 was 16.0% in DR group and 4.3% in DWR group, 45.7% in TT genotype DR group and 58.7% in DWR group (P = 0.025, 0.05). The allele C frequency was 35.2% in DR group and 22.8% in DWR group (P = 0.011, 0.05). The risk of DR in diabetic patients with rs833061CC genotype was higher than that of rs833061TT genotype and TC gene. The carriers were 4.21 times higher (OR=4.21).
There was no significant difference in genotype frequency and allele frequency between the study group and the control group (P 0.05). There was no significant difference in the risk of DR between diabetic patients with rs13207351GG genotype, GA genotype and AA genotype.
The distribution frequency of CC genotype was 21.0% in DR group and 9.8% in DWR group, 28.4% in GG genotype DR group, 42.4% in DWR group (P = 0.049, 0.05), and 46.3% in DR group and 33.4% in DWR group. The carriers were 2.45 times higher (OR=2.45).
There was no significant difference in genotype frequency and allele frequency between the study group and the control group (P 0.05). There was no significant difference in the incidence of DR among diabetic patients with rs3025039CC genotype, CT genotype and TT genotype.
(3) total VEGF protein, VEGF165 content and VEGF165b content:
1) The total level of serum VEGF in normal control group was 44.47 (+ 3.42) (pg / ml), 57.74 (+ 11.23) (pg / ml) in DWR group, 59.25 (+ 11.62) (pg / ml) in DR group, and increased in DWR group and DR group compared with normal control group (P 0.05), but there was no significant difference between DWR group and DR group (P 0.05).
2) The content of VEGF 165 in normal control group was 15.89 (+ 1.31) (pg/ml), 22.68 (+ 4.52) (pg/ml) in DWR group, 27.43 (+ 7.29) (pg/ml) in DR group, and there was significant difference between DWR group and DR group (P = 0.025).
3) The levels of VEGF 165b in blood were 9.25 (+ 0.82) (pg/ml) in the normal control group, 6.97 (+ 1.46) (pg/ml) in the DWR group, and 5.43 (+ 2.35) (pg/ml) in the DR group. The levels of VEGF 165b decreased gradually among the three groups, and the difference was statistically significant (P 0.05). The ratios of VEGF 165 and VEGF 165b changed among the three groups, and gradually increased (1.72, 3.25, 5.05).
4) Total protein and gene locus: The content of VEGF protein in serum of the population with rs2010963CC genotype was significantly higher than that of GG genotype and GA genotype (the content of VEGF protein in CC genotype was 62.59 [13.71], that of GA genotype was 53.27 [10.37], and that of GG genotype was 50.85 [10.59], that of CC genotype and GG genotype and GC genotype were significantly higher than that of the population with rs2010963CC genotype and GA genotype. Genotype comparison showed significant difference (P 0.05), and there was no significant difference among other SNP loci (P 0.05).
(4) predisposing factors of diabetic retinopathy:
1) The data of demographic characteristics and biochemical indexes between DWR group and DR group were tested by T-test in groups. The results showed that there were significant differences in systolic blood pressure, diastolic blood pressure, glycosylated hemoglobin and creatinine between the two groups (P 0.05).
2) Logistic regression analysis: diabetic patients with systolic blood pressure higher than 160 mmHg had a 7.5-fold lower risk of DR than 130 mmHg, diabetic patients with diastolic blood pressure higher than 90 mmHg had a 2-fold higher risk of DR than 90 mmHg, diabetic patients with HbAIC content higher than 14.0% had a 11.50-fold higher risk of DR than 8.0% and high creatinine value. The risk of DR was 5.5 times lower in diabetics with 100 mmol/L than in patients with 60 mmol/L. The risk of DR was 3.2 times higher in diabetics with rs2010963CC gene than in patients with GG genotype. The risk of DR in 5.0 mmol/L diabetic patients was significantly lower than that in 5.0 mmol/L diabetic patients (OR = 0.013). VEGF 165b has a protective effect on diabetic patients.
Conclusion:
(1) The co-dominant model (C A Vs C), recessive model (CC Vs GC+GG) and co-dominant model (TT Vs CC) of VEGF rs699947 and recessive model (TT Vs CT+CC) of VEGF rs3025039 were associated with diabetic retinopathy in yellow people, but the above polymorphisms were not associated with diabetic retinopathy in white people. Customs.
(2) The polymorphism of rs699947, rs833061 and rs2010963 of vascular endothelial growth factor gene may play an important role in the development of diabetic retinopathy.
(3) The change of the ratio of VEGF XXX to EGF xxxb leads to the occurrence and development of diabetic retinopathy. The change of rs2010963 polymorphism is a functional change, which is important for diabetic retinopathy.
(4) Systolic blood pressure (> 160mmHg) diastolic blood pressure (> 90mmHg), glycosylated hemoglobin (> 8.0mmol/L), creatinine (> VEGF 16528mmol/L), rs2010963CC genotype and VEGF 165b5.0mmol/L are high risk groups for diabetic retinopathy.
【学位授予单位】：中南大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R587.2;R774.1
【参考文献】
相关期刊论文 前2条
1 伍春荣;马志中;胡莲娜;许樟荣;任正洪;;糖尿病视网膜病变相关因素的因子分析[J];国际眼科杂志;2007年04期
2 李清解,谢平,黄建军,谷亚鹏,曾卫民,宋惠萍;中国人2型糖尿病患者醛糖还原酶基因5调控区的多态性与功能(英文)[J];Chinese Medical Journal;2002年02期
，本文编号：2194513
本文链接：https://www.wllwen.com/yixuelunwen/yank/2194513.html
最近更新
教材专著
