Dataset Information

Gene set enrichment analysis of pathways and transcription factors associated with diabetic retinopathy using a microarray dataset.

ABSTRACT: Diabetic retinopathy (DR) is a serious microvascular complication of diabetes, which causes visual disability and blindness. Several studies have used gene expression profiling of DR to identify the key genes involved in this process; however, few studies have focused on the associated pathways and transcription factors (TFs), or on the co-expression patterns at the multiple pathways level. In this study, we employed a microarray dataset from the public database library of the Gene Expression Omnibus (GEO) associated with DR and applied gene set enrichment analysis (GSEA) to this dataset and performed candidate TF selection. As a result, 10 upregulated pathways, including the type I diabetes mellitus and peroxisome proliferator-activated receptor (PPAR) signaling pathways, as well as 59 downregulated pathways, including the ErbB signaling pathway and the mammalian target of rapamycin (mTOR) signaling pathway, were identified as DR‑related pathways. The majority of these pathways have been previously identified, but some were novel. Finally, co-expression networks of related pathways were constructed using the significant core genes and TFs, such as PPARγ and SMAD4. The results of our study may enhance our understanding of the molecular mechanisms associated DR at the genome-wide level.

SUBMITTER: He K

PROVIDER: S-EPMC4494587 | biostudies-other | 2015 Jul

REPOSITORIES: biostudies-other

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Gene set enrichment analysis of pathways and transcription factors associated with diabetic retinopathy using a microarray dataset.

He Kan K Lv Wenwen W Zhang Qing Q Wang Yuqing Y Tao Liming L Liu Dahai D

International journal of molecular medicine 20150522 1

Diabetic retinopathy (DR) is a serious microvascular complication of diabetes, which causes visual disability and blindness. Several studies have used gene expression profiling of DR to identify the key genes involved in this process; however, few studies have focused on the associated pathways and transcription factors (TFs), or on the co-expression patterns at the multiple pathways level. In this study, we employed a microarray dataset from the public database library of the Gene Expression Om ...[more]

PMID: 25997411

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Project description:ImportanceDiabetic retinopathy (DR) is a leading cause of vision loss worldwide. As the incidence of both type 1 and type 2 diabetes among youths continues to increase around the world, understanding the factors associated with the development of DR in this age group is important.ObjectiveTo identify factors associated with DR among children, adolescents, and young adults with type 1 or type 2 diabetes in the US.Design, setting, and participantsThis cross-sectional study pooled data from 2 large academic pediatric centers in the US (Baylor College of Medicine/Texas Children's Hospital [BCM/TCH] Diabetes and Endocrine Care Center and Johns Hopkins University [JHU] Pediatric Diabetes Center) to form a diverse population for analysis. Data were collected prospectively at the JHU center (via point-of-care screening using fundus photography) from December 3, 2018, to November 1, 2019, and retrospectively at the BCM/TCH center (via electronic health records of patients who received point-of-care screening using retinal cameras between June 1, 2016, and May 31, 2019). A total of 1640 individuals aged 5 to 21 years with type 1 or type 2 diabetes (308 participants from the JHU center and 1332 participants from the BCM/TCH center) completed DR screening and had gradable images.Main outcome and measuresPrevalence of DR, as identified on fundus photography, and factors associated with DR.ResultsAmong 1640 participants (mean [SD] age, 15.7 [3.6] years; 867 female individuals [52.9%]), 1216 (74.1%) had type 1 diabetes, and 416 (25.4%) had type 2 diabetes. A total of 506 participants (30.9%) were Hispanic, 384 (23.4%) were non-Hispanic Black or African American, 647 (39.5%) were non-Hispanic White, and 103 (6.3%) were of other races or ethnicities (1 was American Indian or Alaska Native, 50 were Asian, 1 was Native Hawaiian or Pacific Islander, and 51 did not specify race or ethnicity, specified other race or ethnicity, or had unavailable data on race or ethnicity). Overall, 558 of 1216 patients (45.9%) with type 1 diabetes used an insulin pump, and 5 of 416 patients (1.2%) with type 2 diabetes used an insulin pump. Diabetic retinopathy was found in 57 of 1640 patients (3.5%). Patients with DR vs without DR had a greater duration of diabetes (mean [SD], 9.4 [4.4] years vs 6.6 [4.4] years; P < .001) and higher hemoglobin A1c (HbA1c) levels (mean [SD], 10.3% [2.4%] vs 9.2% [2.1%]; P < .001). Among those with type 1 diabetes, insulin pump use was associated with a lower likelihood of DR after adjusting for race and ethnicity, insurance status, diabetes duration, and HbA1c level (odds ratio [OR], 0.43; 95% CI, 0.20-0.93; P = .03). The likelihood of having DR was 2.1 times higher among Black or African American participants compared with White participants (OR, 2.12; 95% CI, 1.12-4.01; P = .02); this difference was no longer significant after adjusting for duration of diabetes, insurance status, insulin pump use (among patients with type 1 diabetes only), and mean HbA1c level (type 1 diabetes: OR, 1.79; 95% CI, 0.83-3.89; P = .14; type 2 diabetes: OR, 1.08; 95% CI, 0.30-3.85; P = .91).Conclusions and relevanceThis study found that although the duration of diabetes and suboptimal glycemic control have long been associated with DR, insulin pump use (among those with type 1 diabetes) was independently associated with a lower likelihood of DR, which is likely owing to decreased glycemic variability and increased time in range (ie, the percentage of time blood glucose levels remain within the 70-180 mg/dL range). Black or African American race was found to be associated with DR in the univariable analysis but not in the multivariable analysis, which may represent disparities in access to diabetes technologies and care.

Project description:BackgroundCurrently 93 million people are estimated as living with diabetic retinopathy worldwide. The prevalence and risk factors of diabetic retinopathy in developed countries have been well documented; but in Ethiopia, data on prevalence and associated factors of diabetic retinopathy is lacking.ObjectiveTo determine prevalence and factors associated with development of diabetic retinopathy among diabetic patients at Arbaminch General Hospital, Ethiopia.MethodCross-sectional study design with record review of 400 diabetic patients was conducted at Arbaminch General Hospital from November to January 2015. Among 400 diabetic patients, 270 patients with baseline information and without history of hypertension at baseline were included in this study. But patients with gestational diabetes and with retinopathy at baseline were excluded from the study. Consecutive sampling technique was applied to select study participants. Data of cohorts was extracted from medical record using pre tested structured extraction check list. Data cleaning, coding, categorizing, merging and analysis carried out by STATA version 12. Descriptive statistics was done and presented accordingly. Bivariate binary logistic regression analysis was done to select potential candidates for the full model at P-value cutoff point ≤ 0.25 and multivariable binary logistic regression analysis was made to estimate the independent effect of predictors on the occurrence of diabetic retinopathy. Model diagnostic tests were done, final model fitness was checked using Hosmer and Lemeshow chi square test. Finally, statistical significance was tested at P-value <0.05.ResultPrevalence of diabetic retinopathy among diabetic patients at Arbaminch General Hospital was 13%. Adjusted analysis showed that the odds of diabetic retinopathy were statistically and significantly associated with baseline age (AOR = 6.06: 95%CI; 2.42, 15.21), baseline systolic blood pressure level (AOR = 4.38: 95%CI; 1.64, 11.68), family history of diabetes (AOR = 0.22: 95%CI; 0.08, 0.58) and duration of diabetes (AOR = 8.84: 95%CI; 3.56, 12.89).Conclusion and recommendationIn the current study, prevalence of diabetic retinopathy was 13%. Since baseline age ≥60 years, baseline systolic blood pressure level >140 mmhg, duration of diabetes ≥6 years and patients with family history of diabetes were statistically and significantly related with diabetic retinopathy, special care should be given in addition to routine care.

Project description:Objective:To identify factors associated with prevalent diabetic retinopathy (DR) among Chinese American adults with type 2 diabetes mellitus (T2DM), and to compare these factors to ones previously described for a population-based sample of Latinos with a higher DR prevalence. Design:Population-based cross-sectional study. Participants:4582 Chinese Americans aged 50 or older residing in Monterey Park, California. Methods:Participants completed an in-home questionnaire on socio-demographic status and medical history, and a comprehensive clinical eye examination, using the same protocol implemented in the Los Angeles Latino Eye Study. Fundus photographs from 7 Early Treatment Diabetic Retinopathy fields were graded in a masked manner using a modified Airlie House grading system to assess presence and severity of DR. Logistic regression analyses based on a conceptual model of DR risk identified factors associated with prevalent DR. Main Outcome Measures:Odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with DR and vision-threatening DR (VTDR). Results:In total, 238 participants were diagnosed with any DR; 27 of these were classified as having VTDR. Both, any DR and VTDR showed statistically significant positive associations with T2DM duration (OR5-9 years = 1.24, OR10-14 years = 2.07, OR15+years = 3.99), glycosylated hemoglobin (HbA1c) (OR6.5-6.9% = 1.33, OR7-7.9% = 1.86, OR8%+ = 3.22), systolic blood pressure (SBP) (ORper 10mmHg+ = 1.19), and insulin treatment (ORinsulin+ = 2.44). For VTDR, we also found novel associations with antihypertensive drugs (OR: 0.18; 95% CI: 0.06-0.61) and statins (OR: 4.96; 95% CI: 1.60-16.41). Chinese Americans and Latinos had a nearly identical DR probability based on HbA1c and SBP. However, Latinos had a higher DR probability at every year of duration of T2DM (? 5 years). Conclusions:While we observed an overall lower DR prevalence in Chinese Americans than in Latinos (35.8% of individuals with TD2M in Chinese Americans versus 42.0% in Latinos), our data indicate that the impact of increasing HbA1c and SBP on DR probability is incrementally the same in both populations. However, increasing T2DM duration is associated with higher DR probability in Latinos than Chinese Americans, even after controlling for other known predictors. Novel factors associated with VTDR include antihypertensive drugs and statins. However, to determine if these drugs impact VTDR susceptibility, we need longitudinal data and more cases.

Dataset Information

Gene set enrichment analysis of pathways and transcription factors associated with diabetic retinopathy using a microarray dataset.

Publications

Gene set enrichment analysis of pathways and transcription factors associated with diabetic retinopathy using a microarray dataset.

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