Effect of adiponectin level and genetic variation of its receptors on diabetic retinopathy: A case-control study.
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ABSTRACT:
SUBMITTER: Liao WL
PROVIDER: S-EPMC6426570 | biostudies-literature | 2019 Mar
REPOSITORIES: biostudies-literature
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Project description:Proliferative diabetic retinopathy (PDR) is the most severe vision-threatening complication of diabetes. For investigation of genetic association between TCF7L2 and PDR in Caucasian type 2 diabetes mellitus (T2DM) and its functional consequences, 383 T2DM patients with PDR (T2DM-PDR) and 756 T2DM patients without diabetic retinopathy (T2DM-no DR) were genotyped with rs7903146 in TCF7L2. We found that risk allele (T) frequency of rs7903146 was significantly higher in T2DM-PDR patients (allelic P = 2.52E-04). In lymphoblastoid cells induced to undergo endoplasmic reticulum (ER) stress by treatment of tunicamycin, higher fold change of TCF7L2 and VEGFA mRNA levels were observed in rs7903146-TT cells than in rs7903146-CC cells (P = 0.02 for TCF7L2; P = 0.004 for VEGFA), suggesting that ER stress plays a role in PDR pathogenesis. Silencing TCF7L2 resulted in decreased mRNA levels of both TCF7L2 and VEGFA (P < 0.001). Retinas of oxygen-induced retinopathy mice (a model for PDR) had higher TCF7L2 and VEGFA mRNA levels than those of controls (P = 2.9E-04 for TCF7L2; P = 1.9E-07 for VEGFA). Together, data from our study show that TCF7L2-rs7903146 is associated with PDR in Caucasian T2DM and suggest that TCF7L2 promotes pathological retinal neovascularization via ER stress-dependent upregulation of VEGFA.
| S-EPMC3712060 | biostudies-literature
Project description:Diabetic retinopathy (DR) is a serious complication of diabetes, which is fast reaching epidemic proportions worldwide. While tight glycemic control remains the standard of care for preventing the progression of DR, better insights into DR etiology require understanding its genetic basis, which in turn may assist in the design of novel treatments. During the last decade, genomic medicine is increasingly being applied to common multifactorial diseases such as diabetes and age-related macular degeneration. The contribution of genetics to the initiation and progression of DR has been recognized for some time, but the involvement of specific genes and genetic variants remains elusive. Several investigations are currently underway for identifying DR susceptibility loci through linkage studies, candidate gene approaches, and genome-wide association studies. Advent of next generation sequencing and high throughput genomic technologies, development of novel bioinformatics tools and collaborations among research teams should facilitate such investigations. Here, we review the current state of genetic studies in DR and discuss reported findings in the context of biochemical, cell biological and therapeutic advances. We propose the development of a consortium in India for genetic studies with large cohorts of patients and controls from limited geographical areas to stratify the impact of the environment. Uniform guidelines should be established for clinical phenotyping and data collection. These studies would permit identification of genetic loci for DR susceptibility in the Indian population and should be valuable for better diagnosis and prognosis, and for clinical management of this blinding disease.
| S-EPMC4821123 | biostudies-literature
Project description:BackgroundDiabetic Retinopathy is one of the serious complications patients' diabetic patients suffer from. Little is known about which risk factors are associated with this complication. The aim of this study was therefore to identify determinants of Diabetic Retinopathy in Jimma University Medical Center.MethodsA facility-based case-control study was conducted. Cases were Diabetic patients with diabetic retinopathy and who were on follow up at the Jimma University Medical Center while controls were Diabetic patients but free of diabetic retinopathy and who were on follow up at the Jimma University Medical Center. Cases and controls were identified and 311 of them were recruited using systematic random sampling. Data were entered into the Epi-Data version 4.1 and analyzed using SPSS Version 20. Binary Logistic regression analysis was conducted to identify determinants of diabetic retinopathy.ResultA total of 106 cases and 205 controls diabetic participated in the study. Being ≥60 years of age (AOR = 5.04,95%CI: 1.83,13.87),being illiterate (AOR = 7.17, 95% CI: 2.61,19.7), poor adherence to medication (AOR =3: 95% CI: 1.29,6.95),having high systolic blood pressure (AOR = 3.38:95% CI: 1.26,9.05), having family history of Diabetes Mellitus (AOR = 3.95: 95% CI: 1.64,9.54), having other micro vascular complications (AOR = 3.76,95% CI: 1.33,10.66), poor glycemic control (AOR = 9.08, 95%CI: 3.7,22.29), poor cholesterol control (AOR = 0.21, 95%CI: 0.08,0.51) and being anaemic (AOR = 2.8, 95%CI: 1.05,7.47) were the independent determinants of diabetic retinopathy.ConclusionThis study found that poor adherence to medication, being at the age of 60 years and above, being illiterate patients, having high systolic blood pressure, having a family history of Diabetes Mellitus, having other micro vascular complication, poor glycemic control, poor cholesterol control and being anemic patient were the independent determinants of diabetic retinopathy. Therefore, more attention should be given to older age and illiterate patients. Giving more emphasis for patients poorly adhered to anti-diabetic medications and giving advice for diabetic patients with high systolic blood pressure to follow their blood pressure regularly are also vital. Diabetic patients should also control their Blood sugar and blood cholesterol levels to prevent diabetic retinopathy or reduce its further complications.
| S-EPMC7161237 | biostudies-literature
Project description: Not available
| S-EPMC4439213 | biostudies-literature
Project description:PurposeTo compare adiponectin (APN) levels in the serum and aqueous humor (AH) and evaluate their association with the development/progression of diabetic retinopathy (DR).MethodsDiabetic patients with (group 3; n = 59) and without (group 2; n = 39) DR and age- and sex-matched normal subjects (group 1; n = 35) were compared. Duration of diabetes, body mass index, serum HbA1c, vascular endothelial growth factor (VEGF), APN, pentraxin 3 (PTX3), platelet derived growth factor (PDGF), intercellular adhesion molecule-1 (ICAM-1), and APN were measured and analyzed.ResultsOne hundred and thirty-three participants were included. Compared to patients without diabetes, diabetic patients with DR had significantly elevated average serum APN levels (5.99±3.89 μg/ml versus 3.51±1.44 μg/ml, P = 0.002) and average AH APN levels (10.94±11.74 ng/ml versus 3.65±3.33 ng/ml, P<0.001). Serum APN was significantly correlated with AH APN (R = 0.512, P<0.001) and AH VEGF (R = 0.202, P = 0.020). The log serum APN was significantly correlated with intraocular cytokines, including log APN, log VEGF, log ICAM, log leptin, log PTX3, log PDGF, angiopoietin, C-reactive protein, and interleukins (IL)-5 and IL-10 (P<0.001, P = 0.020, P<0.001, P<0.001, P = 0.001, P<0.001, P = 0.008, P = 0.009, P<0.001, and P = 0.046, respectively). Log serum VEGF showed a significant correlation only with log AH VEGF (P = 0.001). Multivariate logistic analysis was performed to evaluate the association of DR progression and cytokine concentrations; log Serum APN and log AH APN showed good correlation with the DR progression in each model.ConclusionsAH APN levels correlated well with DR development and progression. Serum APN could be a better marker for estimating intraocular cytokines, including both intraocular APN and VEGF concentrations in clinical field, than serum VEGF in DR patients.
| S-EPMC8592425 | biostudies-literature
Project description:The level of total adiponectin, a mixture of different adiponectin forms, has been reported associated with breast cancer risk with inconsistent results. Whether the different forms play different roles in breast cancer risk prediction is unclear. To examine this, we measured total and high molecular weight (HMW) adiponectin in a case-control study (1167 sets). Higher circulating HMW adiponectin was negatively associated with breast cancer risk after adjusting for menopausal status and family history of breast cancer (P=0.024). We analyzed the relationship between adiponectin and breast cancer risk in 6 subgroups. Higher circulating HMW adiponectin was also negatively associated with breast cancer risk (P=0.020, 0.014, 0.035) in the subgroups of postmenopausal women, negative family history of breast cancer, BMI>=24.0. Total adiponectin was positively associated with breast cancer (P=0.028) in the subgroup of BMI<=24.0. Higher HMW/total adiponectin ratio was negatively associated with breast cancer (P=0.019) in the subgroup of postmenopausal women. Interestingly, in the subgroup of women with family history of breast cancer, higher circulating total and HMW adiponectin were positively associated with breast cancer risk (P=0.034, 0.0116). This study showed different forms of circulating adiponectin levels might play different roles in breast cancer risk. A higher circulating HMW adiponectin is associated with a decreased breast cancer risk, especially in postmenopausal, without family history of breast cancer or BMI>=24.0 subgroups, whereas higher circulating HMW adiponectin levels is a risk factor in women with a family history of breast cancer. Further investigation of different forms of adiponectin on breast cancer risk is needed.
| S-EPMC4466435 | biostudies-literature
Project description:PurposeTo evaluate the effectiveness of sulodexide for the treatment of hard exudates (HE) in non-proliferative diabetic retinopathy (NPDR).MethodsThis was a randomized, placebo-controlled, multicenter trial involving 130 patients (65 for each group) who had mild-to-moderate NPDR with macular HE. Participants were given a daily dose of either 50 mg sulodexide or a matching dose of placebo orally for 12 months. Main outcome measure was an improvement in HE defined as a decrease in severity by at least two grades on a 10-grade severity scale. This was evaluated by fundus photography over 12-month period.ResultsThe sulodexide group showed significantly greater improvement in HE severity than that shown by the placebo group (39.0 % vs. 19.3 %; chi square, P = 0.005). Logistic regression analysis yielded an odds ratio of 2.790 (95 % confidence interval, 1.155-6.743; P = 0.023) for the effect of treatment once adjustments were made for demographic, prognostic and disease confounders. Intention to treat and per-protocol analysis yielded similar results. Sulodexide's safety was comparable to that of the placebo.ConclusionsOral sulodexide therapy over 12 months improved macular HE in patients with mild-to-moderate NPDR, without leading to detectable adverse events. The study protocol was registered on clinicaltrial.gov under identifier NCT01295775.
| S-EPMC4445329 | biostudies-literature
Project description:Type 2 diabetes mellitus is a complex disease. Our previous study revealed that TRIB3 genetic variations were strongly associated with diabetic vascular complications, although TRIB3 regulation pathways remain poorly understood. We used two extreme treatment groups from a 2 × 2 factorial randomized controlled trial to identify a positive association, which was further validated in patients receiving cross treatment to test the effect of genetic polymorphisms among the different treatment groups. A gene-centric score (GS)-weighted model including the three associated genetic variations TRIB3 rs2295490, ATF6 rs12086247, and SMARCD3 rs58125572 was used. The results of the GS model indicated a 46% reduction in the risk of primary vascular complications in patients bearing more than two risk alleles [hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.38-0.76, p < 0.001], following intensive glucose control treatment when compared with patients who received standard glucose control treatment. Furthermore, these patients benefited from active blood pressure-lowering treatment (HR 0.39, 95% CI 0.24-0.64, p < 0.001). However, no significant difference was observed between the two interventions in patients with fewer than two risk alleles (HR 1.09, 95% CI 0.86-1.39, p = 0.47). These results indicate that genetic variants in these three genes may be useful biomarkers for individualized drug therapy in diabetic patients.
| S-EPMC6297143 | biostudies-literature
Project description:Neovascular eye diseases are a major cause of blindness including retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration in which new vessel formation is driven by hypoxia or metabolic abnormalities affecting the fuel supply. White-adipose-tissue derived adipokines such as adiponectin modulate metabolic responses. Increasing evidence shows that lack of adiponectin may result in retinal neovascularization. Activation of the adiponectin pathway may in turn restore energy metabolism, to suppress the drive for compensatory but ultimately pathological neovessels of retinopathy. In this review, we will summarize our current knowledge of the role of adiponectin in eye diseases of premature infants, diabetic patients as well as the elderly. Further investigations in this field are likely to lead to new preventative approaches for these diseases.
| S-EPMC4885769 | biostudies-literature
Project description:Current genome-wide association studies (GWAS) are moving towards the use of large cohorts of primary cell lines to study a disease of interest and to assign biological relevance to the genetic signals identified. Here, we use a panel of human osteoblasts (HObs) to carry out a transcriptomic survey, similar to recent studies in lymphoblastoid cell lines (LCLs). The distinct nature of HObs and LCLs is reflected by the preferential grouping of cell type-specific genes within biologically and functionally relevant pathways unique to each tissue type. We performed cis-association analysis with SNP genotypes to identify genetic variations of transcript isoforms, and our analysis indicates that differential expression of transcript isoforms in HObs is also partly controlled by cis-regulatory genetic variants. These isoforms are regulated by genetic variants in both a tissue-specific and tissue-independent fashion, and these associations have been confirmed by RT-PCR validation. Our study suggests that multiple transcript isoforms are often present in both tissues and that genetic control may affect the relative expression of one isoform to another, rather than having an all-or-none effect. Examination of the top SNPs from a GWAS of bone mineral density show overlap with probeset associations observed in this study. The top hit corresponding to the FAM118A gene was tested for association studies in two additional clinical studies, revealing a novel transcript isoform variant. Our approach to examining transcriptome variation in multiple tissue types is useful for detecting the proportion of genetic variation common to different cell types and for the identification of cell-specific isoform variants that may be functionally relevant, an important follow-up step for GWAS.
| S-EPMC2719916 | biostudies-literature