ABSTRACT
Epigenetics refers to the changes in gene expression level and function caused by non-genetic sequence changes.It can provide the time,location and mode of the genetic information for the execution of DNA sequences,including DNA methylation,histone modification,non-coding RNA and chromatin remodeling.Studies had shown that epigenetics plays an important role in the development of diabetic retinopathy (DR),and it had been found that epigenetic-related treatment regimens had a certain effect on the treatment of DR through animal experiments and in vitro experiments.It was benefit to regulate the development of diabetes and its complications by depth study of DNA methylation,histone modification,miRNA and metabolic memory.An understanding of changes in gene transcriptional mechanisms at the epigenetic level could help us to further study the prevention and control of diabetes and its complications,and to provide new ideas for treatment.
ABSTRACT
Background Researches showed that elevatory blood glucose level results in long-term damage of cells and tissue,or metabolic memory phenomenon,and manipulation of hyperglycemic memory is a good approach in the prevention of diabetic complications.However,its mechanism is not clear.It is speculated that the pathogenesis of diabetic retinopathy (DR) in diabetic patients may be associated to related mechanisms.Uncoupling proteins (UCPs) can decrease the production of reactive oxygen species (ROS),which may be related to DR.Objective This study was to explore the association between DR and the single nucleotide polymorphisms (SNPs) of UCP genes in Chinese Han population with type 2 diabetes.Methods A cross-sectional study was performed.This study was approved by Ethic Committee of Affiliated First Hospital of Shanghai Jiao Tong University and complied with Declaration of Helsinki,and written informed consent was obtained from each subject prior to any medical examination.One thousand eight hundreds and seventy-five patients with type 2 diabetes mellitus were enrolled in Xinjing district of Shanghai city by cluster sampling from November 2014 to January 2015.The demographic and medical baseline characteristics,ocular examination and laboratory tests were obtained and periphery blood of 2 ml was collected for extraction of DNA.Eight tag SNPs of UCP1,three tag SNPs of UCP2,and seven tag SNPs of UCP3 were selected as marker locus for the detection of genotype by Sequenom Mass ARRAY.Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry platform were used for genotyping.Hardy-Weinberg equilibrium (HWE) analysis,allele and genotype frequencies,haplotype analysis,and association tests for DR and SNPs were performed by SAS and SHEsis software.Results A total of 530 DR patients were checked out from 1 875 subjects with type 2 diabetes mellitus,with the detection rate of 28.27％.rs660339 locn of UCP2 gene and rs1626521,rs668514 locus of UCP3 gene appeared to have low detectable rates,and the secondary allele base frequency of rs632862 in UCP2 gene was ＜0.01 and rs15763 of UCP3 gene was unmatched with HWE,therefore,these locus analysis was not included.In 13 SNPs locus included in the analysis,only 2 SNPs of UCP1 gene were related to DR.Compared with the non-diabetic retinopathy (NDR) patients,the G allele frequency of rs10011540 was increased (P =0.03,OR =1.31,95 ％ confidence interval[CI] =1.03-1.67,and T allele frequency of rs3811787 was decreased (P=0.04,OR=0.86,95％ CI=0.75-0.99) in DR patients.Genotyping detection showed that the C/C and A/A frequencies of rs3811790 in UCP1 gene were significantly more and C/A frequency was less in DR patients than those in NDR patients (all at P＜0.01).The logistic regression analysis indicated an association of SNPs of rs10011540 and rs3811787 with DR independent from glucose and disease duration.Conclusions The SNPs of rs10011540 and rs3811787 locus in UCP1 gene are associated with DR in Chinese type 2 diabetes patients.
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Objective To observe the genetic predisposition of complement C5 gene polymorphisms in proliferative diabetic retinopathy (PDR) in Chongqing Han population.Methods 400 type 2 diabetes (T2D) patients (case group) and 600 age-and sex-matched healthy controls (control group) were enrolled in this study.There were 8 PDR patients in case group.All the subjects were Han ethnic people.The immune-related representative SNP locus of C5 gene including rs2269067,rs7040033,rs7027797 were screened by linkage disequilibrium analysis.Locus rs1017119 was selected by TagSNP and was around the above three loci.Subjects' peripheral venous blood was collected and DNA was extracted.Genotyping was examined by PCR-restriction fragment length polymorphism method.The level of C5 plasma protein was measured by enzyme-linked immunoabsorbent assay.Results The frequency of GG genotype of rs2269067 was significantly increased in PDR patients in cases group compared with controls (Pc=3.4 × 10-5,OR=1.87,95％CI=1.43-2.44;P=3.1 × 10-6).There was no differences in frequency of G,CC and CG genotype of rs2269067 between two groups (P=1.4 × 10-4,1.000,1.0 × 10-6).There were no differences in frequency of G,CC,CG,GG genotype of rs7040033,rs1017119,and rs7027797 between two groups (P＞0.05).The production of C5 plasma protein was significantly increased in case group as compare with control group (P=0.0004).An increased production of C5 plasma protein was observed in rs2269067 GG genotype cases compared to CG or CC cases (P=0.003,0.001).Conclusion C5 rs2269067 GG genotype may be associated with the PDR of T2D in Chongqing Han population.
ABSTRACT
Epigenetic mechanisms influence gene expression and function without modification of the base sequence of DNA and may generate a genetic phenotype.Epigenetic modifications include DNA methylation,histone modifications,and deployment of noncoding RNA.There is growing evidence that epigenetic mechanisms could play a crucial role in the development of diabetic retinopathy (DR).Molecular biological methods which could maintain mitochondrial homeostasis through the regulation of epigenetic mechanisms may prevent the development of DR.Epigenetic-related treatment modalities will become the new direction of targeted therapy for DR.
ABSTRACT
Epigenetic modifications such as DNA methylation,histone post-translational modifications,non-coding RNA are reversible,heritable alterations which are induced by environmental stimuli.Major risk factors of diabetes and diabetic complications including hyperglycemia,oxidative stress and advanced glycation end products,can lead to abnormal epigenetic modifications in retinal vascular endothelial cells and retinal pigment epithelium cells.Epigenetic mechanisms are involved in the pathogenesis of macular edema and neovascularization of diabetic retinopathy (DR),as well as diabetic metabolic memory.The heritable nature of epigenetic marks also plays a key role in familial diabetes mellitus.Further elucidation of epigenetic mechanisms in DR can open the way for the discovery of novel therapeutic targets to prevent DR progression.
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Objective To determine the association of-429T/C and G1704T polymorphisms in the receptor for advanced glycation end products gene with proliferative diabetic retinopathy (PDR).Methods Case-control study.From the Beijing Desheng Diabetic Eye Study cohort of 1467 patients with type 2 diabetes mellitus (T2DM),a total of 97 patients with PDR and 105 diabetic patients without retinopathy (DWR,duration of diabetes 15 years) were included for this study.Questionnaires were collected and general ophthalmologic examinations were performed.Biochemical analysis was conducted.DNA was extracted from peripheral venous blood.The-429T/C and G1704T single nucleotide polymorphisms were detected by the means of PCR-restrication fragment length polymorphisms.Results The frequency distribution of-429T/C in DWR group was 81.0％ in TT,16.1％ in TC,2.9％ in CC.The frequency distribution of-429T/C in PDR group was 77.3％ in TT,20.6％ in TC,2.1％ in CC.There was no significant statistical difference between the two groups (x2 =0.40,P＞0.05).Frequency of the-429T/C minor allele C in the DWR and PDR group were 11.0％ and 12.4％,respectively,with no significant statistical difference between the two groups (x2 =0.20,P＞0.05).The frequency distribution of G1704T in DWR group was 66.7％ in GG,29.5％ in GT,3.8％ in TT.The frequency distribution of G1704T in PDR group was 78.4％ in GG,21.6％ in GT.There was no significant statistical difference between the two groups (x2 =3.44,P＞0.05).Frequency of the G1704T minor allele T in the DWR and PDR group were 18.6 ％ and 10.8 ％,respectively,in which significant difference was found within the two groups (x2 =4.79,OR=1.88,95％CI:1.06-3.33,P＜0.05).Conclusions G1704T polymorphism is associated with PDR presence and 1704G allele may increase the risk of PDR.
ABSTRACT
It is clear that genetic background contributes to the development and progression of diabetic retinopathy (DR).However,the identification of susceptibility loci through candidate gene approaches,linkage disequilibrium analysis of case-control data and genome wide association study is still in its infancy and faces many challenges due to the complexity of the disease itself.China has rich resources of clinical samples.In order to facilitate elucidating the susceptibility genes of DR in China,we look forward multi-disciplinary,multi-regional collaboration studies integrating novel technologies,such as proteomics,metabolomics and next-generation sequencing to analyze gene-gene and gene-environment interaction factors comprehensively.
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Objective To investigate the polymorphism of the vitamin D receptor gene (VDR)TaqⅠin relation to diabetic retinopathy. Method Fragment length discrepant allele specific PCR(FLDAS-PCR) were used to determine VDR genetypes in 158 patients with diabetic retinopathy and in 198 normal subjects. Results The frequency distribution of VDR genotypes in diabetic retinopathy patients was 106 (67.1%) in TT, 33(20.9%) in Tt, 19(12.0%) in tt; and in normal persons was 165 (83.3%) in TT, 23(11.6%) in Tt, 10 (5.1%) in tt. There was a significant difference between diabetic retinopathy patients and normal persons in distribution of VDR gene TaqⅠgenotypes(P