Polymorphisms of the WRN gene and DNA damage of peripheral lymphocytes in age-related cataract in a Han Chinese population

Jiang, Shenghua; Hu, Nan; Zhou, Jing; Zhang, Junfang; Gao, Ruifang; Hu, Jianyan; Guan, Huaijin

doi:10.1007/s11357-013-9512-4

Cited by 26 publications

(24 citation statements)

References 43 publications

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“…The modified comet assay for lymphocytes and LECs was carried out according to the method described by Jiang et al [13], which was based on that initially reported by Singh et al [26]. The freshly prepared cell suspension of lymphocytes or LECs (1 × 10 4 cells) in 50 μl PBS mixed with 100 μl 0.75% low-melting-point agarose in PBS was spread onto slides precoated with 0.75% normal-melting-point agarose.…”

Section: Methodsmentioning

confidence: 99%

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DNA Damage in Lens Epithelial Cells and Peripheral Lymphocytes from Age-Related Cataract Patients

Zhang

Wu²,

Yang³

et al. 2014

Ophthalmic Res

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Background: Oxidative DNA damage may be one of the etiologies of age-related cataract (ARC). We quantified DNA damage in lens epithelial cells (LECs) and peripheral blood lymphocytes of ARC. Methods: A total of 64 patients with different types of ARC and 23 control subjects were enrolled. Fresh LECs and peripheral lymphocytes were collected and DNA damage was evaluated by alkaline comet assay. The percentage of DNA in the tail of comets (%Tail DNA) and the olive tail moment (OTM) were calculated by CASP software. Results: The results showed the %Tail DNA and OTM in LECs and lymphocytes in the overall cataract patient group were significantly higher than those in the control subjects. The %Tail DNA and OTM of LECs and lymphocytes showed no differences among cortical, nuclear and posterior subcapsular cataracts. The %Tail DNA and OTM in LECs were significantly lower than those in lymphocytes but a significant correlation of the DNA damage was found between them. Conclusion: We concluded that DNA damage in lens and peripheral blood lymphocytes increased in ARC. The results imply that local and systemic oxidative DNA damage might play certain roles in ARC pathogenesis.

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Section: Methodsmentioning

confidence: 99%

“…Our previous studies have detected DNA damage of peripheral lymphocytes by comet assay in ARC patients from a population-based study. We found that DNA damage of peripheral lymphocytes was significantly higher in ARC patients and associated with DNA repair gene polymorphisms [11,13,14]. …”

Section: Introductionmentioning

confidence: 99%

DNA Damage in Lens Epithelial Cells and Peripheral Lymphocytes from Age-Related Cataract Patients

Zhang

Wu²,

Yang³

et al. 2014

Ophthalmic Res

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“…Both CNVs and single nucleotide variants in WRN have been associated with age-related cortical cataract in Han Chinese. [58][59][60] In addition to genes involved in hereditary cataract, variations in other candidate genes not directly associated with inherited forms of cataract have been tentatively implicated in agerelated cataract. These include genes that function in antioxidant metabolism (GSTM1, GSTT1), lactose metabolism (LCT), drug metabolism (NAT2), folate metabolism (MTHFR), DNA repair (XPD), lipid/cholesterol transport (APOE), kinesin/microtubule motor transport (KLC1), actin-cytoskeleton regulation (EZR), chaperone activity (HSP70), and ephrin signaling (EFNA5).…”

Section: Genes Associated With Age-related Cataractmentioning

confidence: 99%

Molecular Genetics of Cataract

Shiels

Hejtmancik

2014

Encyclopedia of Life Sciences

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Cataract can be defined as any opacity or cloudiness of the crystalline lens. When there is significant variation of the refractive index of the lens over distances approximating the wavelength of the transmitted light scattering occurs, resulting in opacity or cataract. Thus, transparency of the crystalline lens requires both orderly arrangement of lens cells and high density of the lens protein constituents. Breakdown of the lens micro‐architecture such as cellular disarray and vacuole formation can cause large fluctuations in optical density of the lens, with resultant cataract. Significant concentrations of high molecular weight protein aggregates of 1000 Å or more in size can also contribute to light scattering. Because 90% of soluble lens proteins is composed of lens crystallins, their short‐range ordered packing in a homogeneous phase and the homoeostatic systems that maintain their stability are critical for maintaining lens transparency. Thus, it is not surprising that approximately 44% of cataract families for whom the mutant gene is known show mutations in lens crystallins with 16% in connexins, 12% in transcription factors, 4% in intermediate filament proteins, 5% in membrane proteins, 5% in chaperones or protein degradation or proofreading proteins, and 6% in a mixed group of other genes, the remainder being unknown. Key Concepts: Cataracts are opacities of the eye lens that result from light scattering either by aggregated proteins within lens cells or disarray of the lens cells themselves. Pathogenesis of inherited cataracts serves to identify critically important developmental, metabolic and biological pathways and processes in the eye lens. Although general trends can be seen with the expression pattern of the causative gene and inherited cataract morphology, identical mutations in the same gene can cause different cataract morphologies and mutations in different genes can result in identical cataract phenotypes. In general, congenital cataracts tend to be caused by mutations that severely disrupt the gene product's structure or function and are thus inherited as highly penetrant Mendelian traits. Conversely, the underlying genetic contributors to age‐related cataracts tend to be less severe mutations that merely impair stability or function and require additional compromise by environmental or modifying genetic factors to cause opacity, so they tend to be multifactorial in their inheritance. Lens crystallins make up 90% of the soluble protein of the eye lens and are thus frequent targets for mutations that destabilise them and cause cataracts. α‐Crystallins are molecular chaperones and can bind denatured proteins, thus preventing or delaying the onset of cataracts, and especially of age‐related cataract. Many other genes implicated in cataractogenesis encode gap junction proteins, solute and aqueous transport proteins, cytoskeletal proteins, developmental transcription factors, membrane proteins, chaperones, or other proteins participating in salvage processes, all important for lens cell development and homoeostasis. In multiple instances, including GALK, EPHA2 and CRYAA, mutations resulting in dramatic destabilization of loss of activity cause congenital cataracts, whereas milder changes contribute to age‐related cataracts in the presence of additional genetic and environmental insults over time.

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“…Investigation of WRN, including mutations, deletions and polymorphisms, are performed in a number of tumors and age-related diseases (5). The WRN codon 1367, located in the short arm of chromosome 8, is a single-nucleotide polymorphism (SNP) site (rs1346044), where the allele A-to-G change leads to a cysteine-to-arginine substitution in the WRN protein (5,6). Studies on the WRN Cys1367Arg reported an association with several diseases, such as cataract (6) and bone and soft tissue sarcomas (7); however, to the best of our knowledge, there has been no such investigation for chordoma.…”

Section: Introductionmentioning

confidence: 99%

WRN Cys1367Arg polymorphism is not associated with skull base chordoma

Wang

Feng

et al. 2014

Biomedical Reports

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Skull base chordoma is a rare tumor with unknown risk factors. Werner syndrome, which is caused by a mutation in the WRN gene, is a disease of progeria, resembling the pathological process of aging. The present study aimed to provide data on the possible association between skull base chordoma and the single-nucleotide polymorphism (SNP) rs1346044 of the WRN gene. Between July, 2010 and September, 2012, a total of 65 patients with pathologically confirmed skull base chordoma and 65 control subjects were enrolled in this case-control study. The clinical data of the skull base chordoma patients were documented and the rs1346044 site in all the enrolled subjects was analyzed by sequencing and statistically compared using SPSS software. The A allele was the dominant allele of the rs1346044. The comparisons of genotype distributions and allele frequencies did not reveal any significant difference between the groups [P=0.383, 95% confidence interval (CI): 0.346-1.505]. The clinicopathological factors were assessed and no statistically significant difference was observed. In conclusion, the present study suggested that there is no association between rs1346044 SNP and skull base chordomas, at least in the population analyzed.

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Polymorphisms of the WRN gene and DNA damage of peripheral lymphocytes in age-related cataract in a Han Chinese population

Cited by 26 publications

References 43 publications

DNA Damage in Lens Epithelial Cells and Peripheral Lymphocytes from Age-Related Cataract Patients

DNA Damage in Lens Epithelial Cells and Peripheral Lymphocytes from Age-Related Cataract Patients

Molecular Genetics of Cataract

WRN Cys1367Arg polymorphism is not associated with skull base chordoma

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