Dataset Information

Association of four gene polymorphisms in Chinese Guangxi population with diabetic retinopathy in type 2 diabetic patients

ABSTRACT: Abstracts

Background

Diabetic retinopathy (DR) is one of the most common chronic microvascular complications of diabetes. Many studies have suggested that genetic factors are important in the context of DR. This study evaluated the associations of GWAS (Genome-wide association study) -identified DR-associated SNPs in a Chinese population in Guangxi Province with type 2 diabetes mellitus (T2DM).

Methods

A total of 386 hospitalized T2DM patients without proliferative diabetic retinopathy (PDR) and 316 hospitalized T2DM patients with PDR were included in this case–control study. Four tag SNPs, including rs1800896 in the IL-10 gene, rs2010963 in the VEGFA gene, rs2070600 in the RAGE gene and rs2910164 in the miR-146a gene, were examined using KASP (kompetitive allele specific PCR) genotyping assays.

Results

There were no significant differences in the genotype or allele frequencies of the miR-146a polymorphism (rs2910164) between subjects with PDR and those without DR. The TC genotype of rs1800896 was determined to be associated with an increased risk of PDR (the odds ratio (OR) was 2.366, with a 95% confidence interval (CI) ranging from 1.144 to 4.894). The CG genotypes of rs2010963 was associated with an decreased risk of PDR (the OR was 0.588, with a 95% CI ranging from 0.366 to 0.946). Regarding rs2070600, 2 genotypes (TT and CT) were associated with a decreased risk of PDR (the OR of the TT genotype was 0.180, with a 95% CI ranging from 0.037 to 0.872, and the OR of the CT genotype was 0.448, with a 95% CI ranging from 0.266 to 0.753).

Conclusions

The rs1800896 polymorphisms in the IL-10 gene, rs2010963 in the VEGFA gene and rs2070600 in the RAGE gene are associated with the risk of PDR in the Han Chinese population of Guangxi Province. Our findings provide suggestive evidence that these polymorphisms may be involved in the pathogenesis of PDR and should be investigated further.

SUBMITTER: Jin H

PROVIDER: S-EPMC8555088 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

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.

Project description:The aim of this study was to investigate the association of three single nucleotide polymorphisms in the erythropoietin gene polymorphisms with diabetic retinopathy and additional role of gene-gene interaction on diabetic retinopathy risk. A total of 1193 patients (579 men, 614 women) with type 2 diabetes mellitus were selected, including 397 diabetic retinopathy patients and 796 controls (type 2 diabetes mellitus patients without diabetic retinopathy); the mean age of all participants was 56.7 ± 13.9 years. Three single nucleotide polymorphisms were selected: rs507392, rs1617640, and rs551238. The t-test was used for comparison of erythropoietin protein level erythropoietin levels in patients having different erythropoietin genotypes. Logistic regression model was used to examine the association between three single nucleotide polymorphisms and diabetic retinopathy. Odds ratio (OR) and 95% confident interval (95% CI) were calculated. Generalized multifactor dimensionality reduction was employed to analyze the impact of interaction among three single nucleotide polymorphisms on CVD risk. After covariates adjustment, the carriers of homozygous mutant of three single nucleotide polymorphisms have higher diabetic retinopathy risk than those with wild-type homozygotes, OR (95% CI) were 2.04 (1.12-2.35), 1.87 (1.10-2.41) and 1.15 (1.06-1.76), respectively. Generalized multifactor dimensionality reduction model indicated a significant three-locus model (p = 0.0010) involving rs507392, rs1617640, and rs551238. Overall, the three-locus models had a cross-validation consistency of 10 of 10, and had the testing accuracy of 60.72%. Subjects with TC or CC-TG or GG-AC or CC genotype have the highest diabetic retinopathy risk. In conclusion, our results support an important association of rs507392, rs1617640 and rs551238 minor allele of erythropoietin with increased diabetic retinopathy risk, and additional interaction among three single nucleotide polymorphisms.

Project description:BACKGROUND: Diabetic retinopathy (DR) is classically defined as a microvasculopathy that primarily affects the small blood vessels of the inner retina as a complication of diabetes mellitus (DM).It is a multifactorial disease with a strong genetic component. The aim of this study is to investigate the association of a set of nine candidate genes with the development of diabetic retinopathy in a South Indian cohort who have type 2 diabetes mellitus (T2DM). METHODS: Seven candidate genes (RAGE, PEDF, AKR1B1, EPO, HTRA1, ICAM and HFE) were chosen based on reported association with DR in the literature. Two more, CFH and ARMS2, were chosen based on their roles in biological pathways previously implicated in DR. Fourteen single nucleotide polymorphisms (SNPs) and one dinucleotide repeat polymorphism, previously reported to show association with DR or other related diseases, were genotyped in 345 DR and 356 diabetic patients without retinopathy (DNR). The genes which showed positive association in this screening set were tested further in additional sets of 100 DR and 90 DNR additional patients from the Aravind Eye Hospital. Those which showed association in the secondary screen were subjected to a combined analysis with the 100 DR and 100 DNR subjects previously recruited and genotyped through the Sankara Nethralaya Hospital, India. Genotypes were evaluated using a combination of direct sequencing, TaqMan SNP genotyping, RFLP analysis, and SNaPshot PCR assays. Chi-square and Fisher exact tests were used to analyze the genotype and allele frequencies. RESULTS: Among the nine loci (15 polymorphisms) screened, SNP rs2070600 (G82S) in the RAGE gene, showed significant association with DR (allelic P = 0.016, dominant model P = 0.012), compared to DNR. SNP rs2070600 further showed significant association with DR in the confirmation cohort (P = 0.035, dominant model P = 0.032). Combining the two cohorts gave an allelic P < 0.003 and dominant P = 0.0013). Combined analysis with the Sankara Nethralaya cohort gave an allelic P = 0.0003 and dominant P = 0.00011 with an OR = 0.49 (0.34 - 0.70) for the minor allele. In HTRA1, rs11200638 (G>A), showed marginal significance with DR (P = 0.055) while rs10490924 in LOC387715 gave a P = 0.07. No statistical significance was observed for SNPs in the other 7 genes studied. CONCLUSIONS: This study confirms significant association of one polymorphism only (rs2070600 in RAGE) with DR in an Indian population which had T2DM.