scholarly journals Epigenetic Regulation of Werner Syndrome Gene in Age-Related Cataract

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Xi Zhu ◽  
Guowei Zhang ◽  
Lihua Kang ◽  
Huaijin Guan
Keyword(s):  
Dna Repair ◽  
Histone Modification ◽  
Cpg Island ◽  
Werner Syndrome ◽  
Methylation Status ◽  
Human Lens ◽  
Repair Gene ◽  
Age Related ◽  
Dna Repair Gene ◽  
And Control

Purpose. To examine the promoter methylation and histone modification of WRN (Werner syndrome gene), a DNA repair gene, and their relationship with the gene expression in age-related cataract (ARC) lens.Methods. We collected the lenses after cataract surgery from 117ARC patients and 39 age-matched non-ARC. WRN expression, DNA methylation and histone modification around the CpG island were assessed. The methylation status of Human-lens-epithelium cell (HLEB-3) was chemically altered to observe the relationship between methylation and expression of WRN.Results. The WRN expression was significantly decreased in the ARC anterior lens capsules comparing with the control. The CpG island of WRN promoter in the ARC anterior lens capsules displayed hypermethylation comparing with the controls. The WRN promoter was almost fully methylated in the cortex of ARC and control lens. Acetylated H3 was lower while methylated H3-K9 was higher in ARC anterior lens capsules than that of the controls. The expression of WRN in HLEB-3 increased after demethylation of the cells.Conclusions. A hypermethylation in WRN promoter and altered histone modification in anterior lens capsules might contribute to the ARC mechanism. The data suggest an association of altered DNA repair capability in lens with ARC pathogenesis.

Polymorphisms in the DNA repair gene XRCC1 and age-related disease

2003 ◽  
Vol 124 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Warren Ladiges ◽  
Jesse Wiley ◽  
Alasdair MacAuley
Keyword(s):  
Dna Repair ◽  
Repair Gene ◽  
Related Disease ◽  
Age Related ◽  
Dna Repair Gene

The role of MGMT promotor hypermethylation as a predictive factor for response to temozolomide in recurrent high-grade glioma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 12509-12509
Author(s):  
J. Sadones ◽  
A. Michotte ◽  
C. Chaskis ◽  
P. In ’t Veld ◽  
S. Califice ◽  
...  
Keyword(s):  
Dna Repair ◽  
Dna Methyltransferase ◽  
Mononuclear Cells ◽  
Methylation Status ◽  
High Grade Glioma ◽  
High Grade ◽  
Repair Gene ◽  
Peripheral Blood Mononuclear ◽  
Tissue Samples ◽  
Dna Repair Gene

12509 Background: Epigenetic silencing of the MGMT (O6-methylguanine-DNA methyltransferase) DNA-repair gene by promotor hypermethylation (MGMT-meth) compromises DNA repair of high-grade glioma (HGG) and has been associated with a survival benefit in patients treated with temozolomide (TMZ) for newly diagnosed glioblastoma multiforme (GBM). It remains undetermined if the MGMT-meth status correlates with response to temozolomide at recurrence and whether extended dosing of TMZ (known to deplete MGMT in peripheral blood mononuclear cells) can overcome resistance in unmethylated HGG. Methods: We are investigating the MGMT-meth status on glioma tissue samples collected at diagnosis from 64 patients (pts). Fifty pts were treated at the time of recurrence with conventional TMZ (5 out of 28d regimen) and 14 pts with extended dosing of TMZ (100 mg/m2/d, 21 out of 28d regimen). Following DNA isolation from archival glioma tissues by phenol/chloroform extraction and a bisulphite conversion of genomic DNA, real-time methylation-specific PCR quantification of the methylation status of the MGMT promotor region is performed by OncoMethylome Sciences S.A. (according to OMS proprietary methodology). Results: At present, results have been obtained for 15 pts (13 M/ 2 W, median age: 46y). From 3 pts a biopsy at recurrence was available for analysis. The result was discordant with the MGMT-meth status at diagnosis in 2 pts (1x meth to unmeth and 1x unmeth to meth). Of the 6 (40%) pts with MGMT-meth gliomas, none had immediate progression on TMZ (respectively 4x SD, 1x CR, 1x PR). Of the 9 pts with an unmethylated MGMT promotor, 4 pts had immediate progression on TMZ and 5 pts had SD (of which 4 had been treated with the 21/28d regimen). All pts, except one, with MGMT-meth had a TTP that was above the median of our study population. The two pts with an MGMT-unmeth status that had a TTP above the median had received the extended dosing regimen. Conclusions: Our preliminary data indicate that MGMT promotor hypermethylation at diagnosis might correlate with sensitivity to TMZ in the recurrent setting. Extended dosing of TMZ might be more active against MGMT-unmethylated glioma. Final data from this study will be available for presentation at the meeting. No significant financial relationships to disclose.

scholarly journals DNA Repair Gene Polymorphism and the Risk of Mitral Chordae Tendineae Rupture

2015 ◽  
Vol 2015 ◽  
pp. 1-6
Author(s):  
Aysel Kalayci Yigin ◽  
Mehmet Bulent Vatan ◽  
Ramazan Akdemir ◽  
Muhammed Necati Murat Aksoy ◽  
Mehmet Akif Cakar ◽  
...  
Keyword(s):  
Dna Repair ◽  
Fragment Length Polymorphism ◽  
Control Group ◽  
Chordae Tendineae ◽  
Repair Gene ◽  
Repair Capacity ◽  
Dna Repair Capacity ◽  
Dna Repair Gene ◽  
Increased Risk ◽  
Polymerase Chain

Polymorphisms in Lys939Gln XPC gene may diminish DNA repair capacity, eventually increasing the risk of carcinogenesis. The aim of the present study was to evaluate the significance of polymorphism Lys939Gln in XPC gene in patients with mitral chordae tendinea rupture (MCTR). Twenty-one patients with MCTR and thirty-seven age and sex matched controls were enrolled in the study. Genotyping of XPC gene Lys939Gln polymorphism was carried out using polymerase chain reaction- (PCR-) restriction fragment length polymorphism (RFLP). The frequencies of the heterozygote genotype (Lys/Gln-AC) and homozygote genotype (Gln/Gln-CC) were significantly different in MCTR as compared to control group, respectively (52.4% versus 43.2%,p=0.049; 38.15% versus 16.2%,p=0.018). Homozygote variant (Gln/Gln) genotype was significantly associated with increased risk of MCTR (OR = 2.059; 95% CI: 1.097–3.863;p=0.018). Heterozygote variant (Lys/Gln) genotype was also highly significantly associated with increased risk of MCTR (OR = 1.489; 95% CI: 1.041–2.129;p=0.049). The variant allele C was found to be significantly associated with MCTR (OR = 1.481; 95% CI: 1.101–1.992;p=0.011). This study has demonstrated the association of XPC gene Lys939Gln polymorphism with MCTR, which is significantly associated with increased risk of MCTR.

scholarly journals DNA Repair Gene Polymorphisms and Susceptibility to Urothelial Carcinoma in a Southeastern European Population

2021 ◽  
Vol 28 (3) ◽  
pp. 1879-1885
Author(s):  
Maria Samara ◽  
Maria Papathanassiou ◽  
Lampros Mitrakas ◽  
George Koukoulis ◽  
Panagiotis J. Vlachostergios ◽  
...  
Keyword(s):  
Dna Repair ◽  
Urothelial Carcinoma ◽  
European Population ◽  
Nucleotide Polymorphisms ◽  
Environmental Carcinogens ◽  
Repair Gene ◽  
High Exposure ◽  
Dna Repair Gene ◽  
Increased Risk ◽  
Xrcc3 Thr241met

Single nucleotide polymorphisms (SNPs) in DNA repair genes may predispose to urothelial carcinoma of the bladder (UCB). This study focused on three specific SNPs in a population with high exposure to environmental carcinogens including tobacco and alcohol. A case-control study design was used to assess for presence of XPC PAT +/−, XRCC3 Thr241Met, and ERCC2 Lys751Gln DNA repair gene SNPs in peripheral blood from patients with UCB and healthy individuals. One hundred patients and equal number of healthy subjects were enrolled. The XPC PAT +/+ genotype was associated with a 2-fold increased risk of UCB (OR = 2.16; 95%CI: 1.14–4; p = 0.01). The −/+ and +/+ XPC PAT genotypes were more frequently present in patients with multiple versus single tumors (p = 0.01). No association was detected between ERCC2 Lys751Gln genotypes/alleles, and risk for developing UCB. Presence of the XRCC3 TT genotype (OR = 0.14; 95%CI:0.07–0.25; p < 0.01) and of the T allele overall (OR = 0.26; 95%CI:0.16–0.41; p < 0.01) conferred a protective effect against developing UCB. The XPC PAT −/+ and XRCC3 Thr241Met SNPs are associated with predisposition to UCB. The XPC PAT −/+ SNP is also an indicator of bladder tumor multiplicity, which might require a more individualized surveillance and treatment.

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