The 5-year onset and regression of diabetic retinopathy in Chinese type 2 diabetes patients.
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ABSTRACT:
SUBMITTER: Jin P
PROVIDER: S-EPMC4234658 | biostudies-other | 2014
REPOSITORIES: biostudies-other
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Project description:PurposeTo investigate whether variants in a set of eight candidate genes are associated with diabetic retinopathy (DR) in a cohort of Chinese patients with type 2 diabetes mellitus (T2DM).MethodsCase-control study. Patients with T2DM were recruited from the Desheng community in urban Beijing and assigned into a DR group or diabetic without retinopathy (DWR) group, based on the duration of diabetes and grading of fundus images. Twenty-six single-nucleotide polymorphisms (SNPs) within eight candidate genes, including PPARγ, vascular endothelial growth factor (VEGF) and its receptor kinase insert domain receptor (KDR), erythropoietin, aldose reductase, protein kinase C-β, angiotensin-converting enzyme, and intercellular adhesion molecule 1, were analyzed using the MassARRAY genotyping system.ResultsA total of 500 patients with T2DM (216 with DR and 284 with DWR) were enrolled in the study. Significant associations of DR were noted with genotypes of four SNPs-rs699947 (p<0.001), rs833061 (p = 0.001), rs13207351 (p<0.001), and rs2146323 (p=0.006)--in the VEGF gene and one variant, rs2071559, in the KDR gene (p=0.034). After adjustment for covariates, significant association of DR remained with the homozygous genotype of the minor allele for the SNPs rs699947 (odds ratio [OR] = 3.54, 95% confidence interval [CI]: 1.12-11.19), rs833061 (OR = 3.72, 95% CI: 1.17-11.85), rs13207351 (OR = 3.76, 95% CI: 1.21-11.71), and rs2146323 (OR = 2.8, 95% CI: 1.46-5.37) in the VEGF gene as well as the SNP rs2071559 (OR = 1.62, 95% CI: 1.08-2.41) in the KDR gene. However, only rs699947 and rs13207351 in the VEGF gene remained statistically significant after Bonferroni correction. No associations were found in other genes tested.ConclusionsThese data expanded previous observations on the association of DR with variants in the VEGF gene in Chinese patients with T2DM. Moreover, a possible association between DR and KDR polymorphisms is suggested.
| S-EPMC3945804 | biostudies-literature
Project description:AIM:To investigate the association between a set of six candidate genes and the risk of diabetic retinopathy (DR) in an urban community cohort of Chinese patients with type 2 diabetes mellitus (T2DM). METHODS:A population-based cross-sectional study. The diabetic subjects were recruited from an urban community in Beijing and categorized into groups of proliferative diabetic retinopathy (PDR), non-proliferative diabetic retinopathy (NPDR), or diabetic without any retinopathy (DWR) based on the fundus photography and duration of diabetes. Six candidate genes, including advanced glycation end product specific receptor (AGER), aldose reductase (AKR1B1), inducible nitric oxide synthase (iNOS), pigment epithelium derived factor (PEDF), tumor necrosis factor-alpha (TNF-α), and paraoxonase 1 (PON1), were chosen based on Meta-analysis of genetic association studies for DR and biochemical pathways implicated in DR progression. The allele and genotype distribution of 21 functional single-nucleotide polymorphisms (SNPs) in those 6 candidate genes were investigated using MassARRAY genotyping system. RESULTS:Among 1461 diabetic patients recruited from community, 569 were selected in following genotyping analysis, including 97 patients with PDR, 217 with NPDR, and 255 with DWR. For the promoter variant rs1051993 in AGER gene, the distribution of allele and genotype in PDR group differed from that in DWR group (allele: P=0.011; genotype: P=0.01). Compared with DWR, patients with PDR had lower frequencies of heterozygous genotype GT (9.8% for DWR, 1% for PDR, OR: 0.10, 95%CI: 0.01-0.72) and minor allele T (4.9% for DWR, 0.5% for PDR, OR: 0.10, 95%CI: 0.01-0.75). In multivariate model, the distribution of genotype for rs1051993 in PDR group was significantly different from that in DWR group (GT vs GG: OR: 0.07, 95%CI: 0.01-0.61, P<0.001). No association with DR was observed in other genotyped SNPs. CONCLUSION:The data suggest a significant association of the promoter variant rs1051993 in AGER gene with PDR in Chinese cohort with T2DM.
| S-EPMC7013782 | biostudies-literature
Project description:PurposeThe aim of this study was to investigate variants in UCP2 genes in type 2 diabetes mellitus (DM) and diabetic retinopathy (DR) in Chinese population.Materials and methodsWe conducted a single nucleotide polymorphism-based and haplotype-based case-control study between the variants of UCP2 and DM and between the variants of UCP2 and DR in 479 Chinese patients with type 2 DM and 479 control subjects without DM. Two SNPs (rs660339 and rs659366) were selected as genetic markers.ResultsThe risk allele C at UCP2 rs660339 was closely associated with DM in Chinese population. There was significant difference in rs660339 between DM and controls (P = 0.0016; OR [95%CI] ?= 1.37 (1.14-1.65)). Subjects who were homozygous of the C allele were more likely to develop DM. The frequency of C allele was higher in DM (58%) than in control (51%). But this locus didn't have a definite effect on the onset of non-proliferative diabetic retinopathy (NPDR) (P = 0.44; OR [95%CI] ?= 0.80 (0.56-1.14)) and proliferative diabetic retinopathy (PDR) (P = 1.00; OR [95%CI] ?= 0.99 (0.74-1.34)) comparing to subjects with DM without retinopathy (DWR), respectively. Moreover, the UCP2 rs659366 polymorphism showed no significant difference between DM and control (P = 0.66; OR [95%CI] ?= 1.10 (0.91-1.32)). However, there was a significant difference between PDR and DWR (P = 0.016; OR [95%CI] ?= 0.66 (0.49-0.90)), but there was no difference between NPDR and DWR (P = 1.00; OR [95%CI] ?= 0.96 (0.67-1.37)). Participants who carried the G allele at rs659366 were more likely to develop PDR. For the haplotype, C-A was present more frequently in DM than in control (16% vs 7%), indicating that it was risky, and T-A was present less in DM than in control (29% vs 35%). Haplotype frequencies in DR and DWR showed no significant difference (P = 0.068).ConclusionIt was indicated that UCP2 may be implicated in the pathogenesis of type 2 DM and DR in Chinese population.
| S-EPMC4232517 | biostudies-literature
Project description:Objective This study aimed to explore the relationship between homocysteine (Hcy) and diabetic retinopathy (DR) and the impacts of the Hcy pathway on this relationship against this background. Methods This study retrieved 1979 patients with type 2 diabetes (T2D) from the First Affiliated Hospital of Liaoning Medical University in Jinzhou, Liaoning Province, China. Multiple logistic regression was used to analyze the effects of Hcy cycle on the relationship between Hcy and DR. Spearman’s rank correlation analysis was used to analyze the correlation between risk factors related to DR progression and Hcy. Finally, the results of logistic regression were supplemented by mediation analysis. Results We found there was a negative correlation between low concentration of Hcy and DR (OR : 0.83, 95%CI: 0.69-1). After stratifying all patients by cysteine (Cys) or Methionine (Met), this relationship remained significant only in low concentration of Cys (OR: 0.75, 95%CI: 0.61-0.94). Through the RCS curve, we found that the effect of Hcy on DR presents a U-shaped curve relationship. Mediating effect in Met and Hcy cycles was also significant [Total effect c (OR: 0.968, 95%CI: 0.938-0.998), Direct effect path c’ (OR: 0.969, 95%CI: 0.940-0.999), Path a (OR: 1.047, 95%CI: 1.004-1.091), Path b (OR: 0.964, 95%CI: 0.932-0.998)]. Conclusions The relationship between Hcy and DR presents a U-shaped curve and the homocysteine cycle pathway has an impact on it. And too low concentration of Hcy indicates a lack of other substances, such as vitamins. It is suggested that the progression of DR is the result of a combination of many risk factors. Further prospective studies are needed to determine the role of Hcy in the pathogenesis of DR.
| S-EPMC9276920 | biostudies-literature
Project description:BackgroundDiabetic retinopathy (DR) is an important microvascular complication of diabetes with a high concordance rate in patients with diabetes. Inflammation is supposed to participate in the development of DR. This study aimed to investigate whether genetic variants of CRP are associated with DR.MethodsA total of 1,018 patients with type 2 diabetes were recruited in this study. Of these patients, 618 were diagnosed with DR, 400 were patients with diabetes for over 10 years but without DR, considered as cases and controls for DR, respectively. Four tagging SNPs (rs2808629, rs3093077, rs1130864 and rs2808634) within CRP region were genotyped for all the participants. Fundus photography was performed for diagnosis and classification for DR.Resultsrs2808629 was significantly associated with increased susceptibility to DR (odds ratio 1.296, 95% CI 1.076-1.561, P = 0.006, empirical P = 0.029, for G allele). This association remained significant after adjustment for confounding factors (odds ratio 1.261, 95% CI 1.022-1.555, P = 0.030).ConclusionsIn this study, we found CRP rs2808629 was associated with DR in the Chinese patients with type 2 diabetes.
| S-EPMC4350906 | biostudies-literature
Project description:Purpose:To evaluate neurodegeneration in patients with type 2 diabetes mellitus (DM2) without diabetic retinopathy and to assess the possible role of systemic vascular complications in retinal changes. Methods:Sixty eyes of 60 patients with DM2 and without any signs of diabetic retinopathy and 60 eyes of 60 healthy controls underwent retinal evaluation using Spectralis optical coherence tomography. Macular ganglion cell layer (GCL) and retinal nerve fiber layer (RNFL) were evaluated. Peripapillary RNFL thickness was assessed using Glaucoma and Axonal Analytics applications. Comparison between patients with the presence/absence of systemic vascular complications and different disease duration was made. Results:Macular GCL was reduced in patients compared to controls (p < 0.001). Differences in the macular RNFL thickness were only observed in the outer inferior sector (p=0.033). A reduction in the peripapillary RNFL (average, inferior, and inferotemporal thickness, p < 0.05 for all three) was observed in patients using both applications. Patients with chronic systemic vascular complications presented a reduction in the temporal RNFL (p=0.019) compared to patients without complications. The superotemporal RNFL thickness was thinner in patients with longer disease duration. Conclusions:Patients with type 2 DM without diabetic retinopathy and good metabolic control present neurodegeneration affecting neurons in the macular area and axons in different sectors of the optic disc. Systemic vascular complications contributed to further axonal damage in these patients, suggesting a possible role of subclinical ischaemia to retinal neurodegeneration in type 2 DM.
| S-EPMC6702840 | biostudies-literature
Project description:Diabetic retinopathy (DR) is a common complication of diabetes, and it is the consequence of microvascular retinal changes due to high glucose levels over a long time. Metabolomics profiling is a rapidly evolving method used to identify the metabolites in biological fluids and investigate disease progression. In this study, we used a targeted metabolomics approach to quantify the serum metabolites in type 2 diabetes (T2D) patients. Diabetes patients were divided into three groups based on the status of their complications: non-DR (NDR, n = 143), non-proliferative DR (NPDR, n = 123), and proliferative DR (PDR, n = 51) groups. Multiple logistic regression analysis and multiple testing corrections were performed to identify the significant differences in the metabolomics profiles of the different analysis groups. The concentrations of 62 metabolites of the NDR versus DR group, 53 metabolites of the NDR versus NPDR group, and 30 metabolites of the NDR versus PDR group were found to be significantly different. Finally, sixteen metabolites were selected as specific metabolites common to NPDR and PDR. Among them, three metabolites including total DMA, tryptophan, and kynurenine were potential makers of DR progression in T2D patients. Additionally, several metabolites such as carnitines, several amino acids, and phosphatidylcholines also showed a marker potential. The metabolite signatures identified in this study will provide insight into the mechanisms underlying DR development and progression in T2D patients in future studies.
| S-EPMC7595280 | biostudies-literature
Project description:Extracellular superoxide dismutase (ecSOD) is the major extracellular scavenger of reactive oxygen species and associated with the diabetic complication in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the serum ecSOD activity in Chinese patients with different stages of diabetic retinopathy (DR) and evaluate the association between the serum ecSOD activity and the severity of DR. A total of 343 T2DM patients were categorized into three groups: nondiabetic retinopathy (NDR) group, nonproliferative diabetic retinopathy (NPDR) group, and proliferative diabetic retinopathy (PDR) group. Serum ecSOD activities were measured by the autoxidation of the pyrogallol method. In this study, 271, 46, and 26 patients were enrolled in the NDR, NPDR, and PDR groups, respectively. We found a significantly decreased trend of serum ecSOD activity among NDR subjects (118.0 ± 11.5 U/mL) compared to NPDR subjects (108.5 ± 11.9 U/mL) (P < 0.001) and NPDR subjects compared to PDR subjects (102.7 ± 12.4 U/mL) (P = 0.041). Serum ecSOD activity was an independent risk factor for DR (OR = 0.920, P < 0.001) and was associated with the progression of DR. Serum ecSOD activity might be a biomarker for DR screening and evaluation of the clinical severity of DR in Chinese T2DM patients.
| S-EPMC5937587 | biostudies-literature
Project description:ObjectiveDiabetic nephropathy and retinopathy are two important microvascular diabetes complications with a high concordance rate in diabetic patients. A recent genome-wide association study in type 1 diabetic patients of European descent identified four loci to be associated with diabetic nephropathy. The aim of this study was to test the effects of single nucleotide polymorphisms (SNPs) from these four loci on diabetic nephropathy and retinopathy in Chinese type 2 diabetic patients.Research design and methodsIn stage 1, we recruited 1,276 type 2 diabetic patients, including 378 patients with diabetic nephropathy but no retinopathy, 374 patients with diabetic retinopathy but no nephropathy, 244 patients with both diabetic retinopathy and nephropathy, and 280 control subjects with diabetes for >10 years and no diabetic retinopathy or nephropathy. Fifty-five SNPs from four loci (CPVL/CHN2, FRMD3, CARS, and IRS2) were genotyped. The SNPs that showed associations to diabetic retinopathy or nephropathy were genotyped in stage 2 samples for replication.ResultsSNPs from CPVL/CHN2 and FRMD3 were associated with diabetic retinopathy with rs39059 and rs10868025 as the top SNPs (odds ratio [OR] 1.292, 95% CI 1.097-1.523, P = 0.0022, for rs39059; 1.201, 1.014-1.422, P = 0.0343, for rs10868025) in stage 1 samples. In stage 2 analysis, only rs39059 showed similar effect to diabetic retinopathy (OR 1.269, 0.989-1.628, P = 0.0689), and meta-analysis showed a significant association between rs39059 and diabetic retinopathy, with an OR of 1.285 (1.120-1.474, P = 0.0003). CPVL/CHN2 rs39059 was also associated with levels of diabetic retinopathy (P = 0.0007 for trend). However, no association was detected between these SNPs and diabetic nephropathy.ConclusionsIn this study, we found CPVL/CHN2 rs39059 was associated with diabetic retinopathy in the Chinese type 2 diabetic patients.
| S-EPMC3198055 | biostudies-literature
Project description:Diabetic retinopathy (DR) is a major microvascular complication of diabetes. Susceptibility genes for type 2 diabetes may also impact the susceptibility of DR. This case-control study investigated the effects of 88 type 2 diabetes susceptibility loci on DR in a Chinese population with type 2 diabetes performed in two stages. In stage 1, 88 SNPs were genotyped in 1,251 patients with type 2 diabetes, and we found that ADAMTS9-AS2 rs4607103, WFS1 rs10010131, CDKAL1 rs7756992, VPS26A rs1802295 and IDE-KIF11-HHEX rs1111875 were significantly associated with DR. The association between CDKAL1 rs7756992 and DR remained significant after Bonferroni correction for multiple comparisons (corrected P = 0.0492). Then, the effect of rs7756992 on DR were analysed in two independent cohorts for replication in stage 2. Cohort (1) consisted of 380 patients with DR and 613 patients with diabetes for ≥5 years but without DR. Cohort (2) consisted of 545 patients with DR and 929 patients with diabetes for ≥5 years but without DR. A meta-analysis combining the results of stage 1 and 2 revealed a significant association between rs7756992 and DR, with the minor allele A conferring a lower risk of DR (OR 0.824, 95% CI 0.743-0.914, P = 2.46 × 10-4).
| S-EPMC5562862 | biostudies-literature