Browse
Submit Data
Databases
API
Help

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Potential underlying genetic associations between keratoconus and diabetes mellitus

ABSTRACT: Background Keratoconus (KC) is the most common ectatic corneal disease, characterized by significantly localized thinning of the corneal stroma. Genetic, environmental, hormonal, and metabolic factors contribute to the pathogenesis of KC. Additionally, multiple comorbidities, such as diabetes mellitus, may affect the risk of KC. Main Body Patients with diabetes mellitus (DM) have been reported to have lower risk of developing KC by way of increased endogenous collagen crosslinking in response to chronic hyperglycemia. However, this remains a debated topic as other studies have suggested either a positive association or no association between DM and KC. To gain further insight into the underlying genetic components of these two diseases, we reviewed candidate genes associated with KC and central corneal thickness in the literature. We then explored how these genes may be regulated similarly or differentially under hyperglycemic conditions and the role they play in the systemic complications associated with DM. Conclusion Our comprehensive review of potential genetic factors underlying KC and DM provides a direction for future studies to further determine the genetic etiology of KC and how it is influenced by systemic diseases such as diabetes.

SUBMITTER: Ates K

PROVIDER: S-EPMC8570550 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Underlying genetic models of inheritance in established type 2 diabetes associations.

Project description:For most associations of common single nucleotide polymorphisms (SNPs) with common diseases, the genetic model of inheritance is unknown. The authors extended and applied a Bayesian meta-analysis approach to data from 19 studies on 17 replicated associations with type 2 diabetes. For 13 SNPs, the data fitted very well to an additive model of inheritance for the diabetes risk allele; for 4 SNPs, the data were consistent with either an additive model or a dominant model; and for 2 SNPs, the data were consistent with an additive or recessive model. Results were robust to the use of different priors and after exclusion of data for which index SNPs had been examined indirectly through proxy markers. The Bayesian meta-analysis model yielded point estimates for the genetic effects that were very similar to those previously reported based on fixed- or random-effects models, but uncertainty about several of the effects was substantially larger. The authors also examined the extent of between-study heterogeneity in the genetic model and found generally small between-study deviation values for the genetic model parameter. Heterosis could not be excluded for 4 SNPs. Information on the genetic model of robustly replicated association signals derived from genome-wide association studies may be useful for predictive modeling and for designing biologic and functional experiments.

| S-EPMC2732984 | biostudies-literature

Associations between diabetes mellitus and pulmonary hypertension in chronic respiratory disease patients.

Project description:BACKGROUND:Pulmonary hypertension (PH) is a common complication of chronic respiratory disease. Recent studies have reported diabetes mellitus (DM) to be a poor prognostic factor in patients with chronic respiratory disease, including chronic obstructive pulmonary disease or interstitial pneumoniae. However, the association between DM and PH in chronic respiratory disease remains unclear. In this study, we aimed to investigate whether DM is a predictor of PH in patients with chronic respiratory disease. METHODS:We prospectively analyzed 386 patients in our hospital with chronic respiratory disease. An echocardiographic pressure gradient between the right atrium and the right ventricle of ? 40 mmHg was defined as PH. We compared the clinical characteristics and impact of DM between chronic respiratory disease patients with and those without PH. RESULTS:Of the 386 patients, 42 (10.9%) were diagnosed as having PH. The PH group had higher modified medical research council (mMRC) grade and complication rate of DM, but not hypertension and hyperlipidemia, when compared to the non-PH group. Multivariable logistic regression analysis revealed that mMRC scale (odds ratio 1.702, 95% confidence interval, 1.297 to 2.232, P < 0.001) and presence of DM (odd ratio 2.935, 95% confidence interval, 1.505 to 5.725, P = 0.002) were associated with PH in chronic respiratory disease patients. CONCLUSION:DM is potentially associated with PH and is an independent factor for prediction of PH in patients with chronic respiratory disease.

| S-EPMC6177140 | biostudies-other

Associations between Aquaglyceroporin Gene Polymorphisms and Risk of Type 2 Diabetes Mellitus.

Project description:Objectives:AQP7 and AQP9 represent glycerol channel in adipose tissue and liver and have been associated with metabolic diseases. We aimed to investigate the associations between genetic variants in AQP7 and AQP9 genes and the risk of type 2 diabetes (T2DM) in Chinese population. Methods:Blood samples were drawn from 400 T2DM patients and 400 age- and gender-matched controls. Genomic DNA was extracted by proteinase K digestion and phenol-chloroform extraction. Genotyping of 5 single nucleotide polymorphisms (SNPs) in AQP7 (rs2989924, rs3758269, and rs62542743) and AQP9 (rs57139208, rs16939881) was performed by the polymerase chain reaction assay with TaqMan probes. Results:The subjects with rs2989924 GA+AA genotypes had 1.47-fold increased risk of T2DM (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.06-2.04), compared to those with GG genotype, and this association remained significant after adjustment for covariates (OR 1.66, 95% CI 1.07-2.57). When compared with rs3758269 CC genotype, the subjects with CT+TT genotypes had 45% decreased T2DM risk after multivariate adjustment (OR 0.55, 95% CI 0.35-0.85). The associations were evident in elder and overweight subjects and those with central obesity. No association was observed between AQP9 SNPs and T2DM risk. Conclusions:AQP7 SNP rs2989924 and rs3758269 were associated with T2DM risk in Chinese Han population.

| S-EPMC6288565 | biostudies-literature

Project description:BackgroundThe age- and sex-related differences on the impacts of body composition on diabetes mellitus (DM) remain uncertain.MethodsThe fourth and fifth Korea National Health and Nutrition Examination Survey included 15,586 subjects over 30 years of age who completed dual-energy X-ray absorptiometry. We conducted a cross-sectional study to investigate whether muscle mass index (MMI), defined as appendicular skeletal muscle divided by body mass index (BMI), and fat mass index (FMI), defined as trunk fat mass divided by BMI, were differently associated with DM according to age and sex.ResultsIn multivariate logistic regression, the risk for DM significantly increased across quartiles of FMI in men aged ≥70. Meanwhile, MMI showed a protective association with DM in men of the same age. The odds ratios (ORs) for the highest quartile versus the lowest quartile of FMI and MMI were 3.116 (95% confidence interval [CI], 1.405 to 6.914) and 0.295 (95% CI, 0.157 to 0.554), respectively. In women, the ORs of DM was significantly different across FMI quartiles in those over age 50. The highest quartile of FMI exhibited increased ORs of DM in subjects aged 50 to 69 (OR, 1.891; 95% CI, 1.229 to 2.908) and ≥70 (OR, 2.275; 95% CI, 1.103 to 4.69) compared to lowest quartile. However, MMI was not significantly associated with DM in women of all age groups.ConclusionBoth FMI and MMI were independent risk factors for DM in men aged 70 years or more. In women over 50 years, FMI was independently associated with DM. There was no significant association between MMI and DM in women.

| S-EPMC8024156 | biostudies-literature

European versus Asian differences for the associations between paraoxonase-1 genetic polymorphisms and susceptibility to type 2 diabetes mellitus.

Project description:Many studies have examined the associations between paraoxonase-1 (PON1) genetic polymorphisms (Q192R, rs662 and L55M, rs854560) and the susceptibility to type 2 diabetes mellitus (T2DM) across different ethnic populations. However, the evidence for the associations remains inconclusive. In this study, we performed a meta-analysis to clarify the association of the two PON1 variants with T2DM risk. We carried out a systematic search of PubMed, Embase, CNKI and Wanfang databases for studies published before June 2017. The pooled odds ratios (ORs) for the association and their corresponding 95% confidence intervals (CIs) were calculated by a random- or fixed-effect model. A total of 50 eligible studies, including 34 and 16 studies were identified for the PON1 Q192R (rs662) and L55M (rs854560) polymorphism, respectively. As for the PON1 Q192R polymorphism, the 192R allele was a susceptible factor of T2DM in the South or East Asian population (OR > 1, P < 0.05) but represented a protective factor of T2DM in European population (OR = 0.66, 95% CI = 0.45-0.98) under a heterozygous genetic model. With regard to the PON1 L55M polymorphism, significant protective effects of the 55M allele on T2DM under the heterozygous (OR = 0.77, 95% CI = 0.61-0.97) and dominant (OR = 0.80, 95% CI = 0.65-0.99) genetic models were found in the European population, while no significant associations in the Asian populations under all genetic models (P > 0.05). In summary, by a comprehensive meta-analysis, our results firmly indicated that distinct effects of PON1 genetic polymorphisms existed in the risk of T2DM across different ethnic backgrounds.

| S-EPMC5824408 | biostudies-literature

Genetic associations for keratoconus: a systematic review and meta-analysis.

Project description:Genetic associations for keratoconus could be useful for understanding disease pathogenesis and discovering biomarkers for early detection of the disease. We conducted a systematic review and meta-analysis to summarize all reported genetic associations for the disease. We searched in the MEDLINE, Embase, Web of Science, and HuGENET databases for genetic studies of keratoconus published from 1950 to June 2016. The summary odds ratio and 95% confidence intervals of all polymorphisms were estimated using the random-effect model. Among 639 reports that were retrieved, 24 fulfilled required criteria as eligible studies for meta-analysis, involving a total of 53 polymorphisms in 28 genes/loci. Results of our meta-analysis lead to the prioritization of 8 single-nucleotide polymorphisms (SNPs) in 6 genes/loci for keratoconus in Whites. Of them 5 genes/loci were originally detected in genome-wide association studies, including FOXO1 (rs2721051, P?=?5.6?×?10-11), RXRA-COL5A1 (rs1536482, P?=?2.5?×?10-9), FNDC3B (rs4894535, P?=?1.4?×?10-8), IMMP2L (rs757219, P?=?6.1?×?10-7; rs214884, P?=?2.3?×?10-5), and BANP-ZNF469 (rs9938149, P?=?1.3?×?10-5). The gene COL4A4 (rs2229813, P?=?1.3?×?10-12; rs2228557, P?=?4.5?×?10-7) was identified in previous candidate gene studies. We also found SNPs in 10 genes/loci that had a summary P value?<?0.05. Sensitivity analysis indicated that the results were robust. Replication studies and understanding the roles of these genes in keratoconus are warranted.

| S-EPMC5496893 | biostudies-literature

Genetic and epigenetic mechanisms underlying arsenic-associated diabetes mellitus: a perspective of the current evidence.

Project description:Chronic exposure to arsenic has been associated with the development of diabetes mellitus (DM), a disease characterized by hyperglycemia resulting from dysregulation of glucose homeostasis. This review summarizes four major mechanisms by which arsenic induces diabetes, namely inhibition of insulin-dependent glucose uptake, pancreatic ?-cell damage, pancreatic ?-cell dysfunction and stimulation of liver gluconeogenesis that are supported by both in vivo and in vitro studies. Additionally, the role of polymorphic variants associated with arsenic toxicity and disease susceptibility, as well as epigenetic modifications associated with arsenic exposure, are considered in the context of arsenic-associated DM. Taken together, in vitro, in vivo and human genetic/epigenetic studies support that arsenic has the potential to induce DM phenotypes and impair key pathways involved in the regulation of glucose homeostasis.

| S-EPMC5480787 | biostudies-literature

Associations between urate-lowering therapy and the risk of type 2 diabetes mellitus.

Project description:BackgroundGout is independently associated with increased risk of type 2 diabetes mellitus (T2DM). Urate-lowering therapy (ULT) might be beneficial in lowering the risks of T2DM. Therefore, we conducted a nested case-control study to evaluate the associations between ULT and T2DM.MethodsThis study retrieved the data of 29,765 gout patients from the period of 1998-2010 by using data from Taiwan's National Health Insurance Research Database. Controls (n = 59,530) were matched at a 1:2 ratio by age, sex, and region. Multivariate Cox proportional hazards regression were performed to examine the dose-dependent relationship between ULT and T2DM.ResultsThe adjusted Hazard ratio (HR) for the association of T2DM with allopurinol or benzbromarone exposure was 1.17 (95% confidence interval (CI) 1.07-1.28) and1.09 (95% CI 1.03-1.15), respectively. The HR for the cumulative allopurinol dose was 0.87 (95% CI 0.71-1.07) for patients with dose ?1.3 mg/day and was 1.31 (95% CI 1.13-1.52) for those with a dose >15.2 mg/day. Similarly, the HR for the cumulative benzbromarone dose was 0.85(95% CI 0.75-0.96) for patients with a dose ?1.3 mg/day and 1.42 (95% CI 1.30-1.55) for patients with a dose>9.4 mg/day, respectively. Moreover, the average exposure dose of >100 mg/day for allopurinol and >100 mg/day for benzbromarone was associated with a 1.28-fold (95% CI 1.11-1.48) and 1.47-fold (95% CI 1.23-1.76) T2DM risk respectively. The HR for patients in aged >50 years group with cumulative dose ?1.3 mg/day of allopurinol or benzbromarone had lower risk of T2DM (HR = 0.74, 95% CI 0.58-0.94 for allopurinol; HR = 0.79, 95% CI 0.69-0.90 for benzbromarone).ConclusionGout patients with prolonged ULT and a high dose of ULT were associated with a significant increase in T2DM risk. Although gout patients with age greater than 50 years and a lower dose of ULT may be beneficial in lowering T2DM risk, further clinical studies need to be confirmed these associations.

| S-EPMC6322774 | biostudies-literature

Molecular and Electrophysiological Mechanisms Underlying Cardiac Arrhythmogenesis in Diabetes Mellitus.

Project description:Diabetes is a common endocrine disorder with an ever increasing prevalence globally, placing significant burdens on our healthcare systems. It is associated with significant cardiovascular morbidities. One of the mechanisms by which it causes death is increasing the risk of cardiac arrhythmias. The aim of this article is to review the cardiac (ion channel abnormalities, electrophysiological and structural remodelling) and extracardiac factors (neural pathway remodelling) responsible for cardiac arrhythmogenesis in diabetes. It is concluded by an outline of molecular targets for future antiarrhythmic therapy for the diabetic population.

| S-EPMC5011530 | biostudies-other

Genetic associations between Transcription Factor 7 Like 2 rs7903146 polymorphism and type 2 diabetes mellitus: a meta-analysis of 115,809 subjects.

Project description:Background:Some genetic association studies tried to investigate potential associations of Transcription Factor 7 Like 2 (TCF7L2) rs7903146 polymorphism with type 2 diabetes mellitus (T2DM). However, the results of these studies were not consistent. Thus, we performed the present meta-analysis to explore associations between TCF7L2 rs7903146 polymorphism and T2DM in a larger pooled population. Methods:Systematic literature research of PubMed, Web of Science and Embase was performed to identify eligible studies for pooled analyses. I2 statistics were employed to assess between-study heterogeneities. If I2 was greater than 50%, random-effect models (REMs) would be used to pool the data. Otherwise, fixed-effect models (FEMs) would be applied for synthetic analyses. Results:Totally 68 studies with 115,809 subjects were included for analyses. The pooled analyses showed that TCF7L2 rs7903146 (dominant model: p?<?0.0001; recessive model: p?<?0.0001; over-dominant model: p?<?0.0001; allele model: p?<?0.0001) polymorphism was significantly associated with susceptibility to T2DM in overall population. Further subgroup analyses revealed similar significant findings in both Asians and Caucasians. Conclusions:In conclusion, our findings supported that TCF7L2 rs7903146 polymorphism could be used to identify individuals at high risk of developing T2DM in Asians and Caucasians.

| S-EPMC6612193 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data