The Associations between Single Nucleotide Polymorphisms of DNA Repair Genes, DNA Damage, and Age-Related Cataract: Jiangsu Eye Study

Su, Shih Bin; Yao, Yong; Zhu, Rongrong; Liang, Congkai; Jiang, Shenghua; Hu, Nan; Zhou, Jing; Yang, Mei; Xing, Qinghe; Guan, Huaijin

doi:10.1167/iovs.12-10940

Cited by 37 publications

(40 citation statements)

References 35 publications

(28 reference statements)

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“…The biomarker of oxidative DNA damage, 8-hydroxydeoxyguanosine (8-OHdG), significantly increased in leukocytes and serum of cataract patients [4,5]. Recently, several studies reported the association between genetic polymorphisms of antioxidant enzymes/DNA repair enzymes [7,8,9,10,11] and ARC. The genetic factors influencing the functional integrity of the human lens are important to keep it transparent even at old age [12].…”

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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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: 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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“…11 One rural district/county within southern and northern Jiangsu was selected as the sampling area, which are Binhu District and Funing County, respectively. The surveys were carried out by randomly selecting individuals within each district/county which was similar with the method we described previously.…”

Section: Methodsmentioning

confidence: 99%

“…Details of ocular examination, blood collection, and DNA extraction have been reported previously. 11 …”

Section: Methodsmentioning

confidence: 99%

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Association of ZNF644, GRM6, and CTNND2 genes with high myopia in the Han Chinese population: Jiangsu Eye Study

Wang

Yang

et al. 2016

Eye

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Aims High myopia is a common visual disorder in the world. The ZNF644, GRM6, and CTNND2 genes are expressed in the retina. This study aims to investigate the associations of these genes with high myopia in Han Chinese population. Methods The case-control association included high myopia cases (n = 430) and controls (n = 430) recruited from a populationbased study, 'Jiangsu Eye Study'. Fourteen single-nucleotide polymorphisms (SNPs) in three genes were genotyped by the TaqMan method using the real-time PCR system. Results Three SNPs GRM6-rs11746675, GRM6-rs2067011, and GRM6-rs2645339 were associated with high myopia (odds ratio (OR) = 0.74, P = 0.003; OR = 0.78, P = 0.018; and OR = 0.78, P = 0.023; respectively). The significances of rs2067011 and rs2645339 disappeared after multiple testing corrections. Rs11746675 remained significant after correction for multiple testing. The genetic model analysis found that GRM6-rs11746675 and GRM6-rs2067011 were suggestively associated with high myopia in the recessive model (OR = 0.54, P = 0.004; OR = 0.52, P = 0.003; respectively). Haplotype GAT for GRM6 markers rs2067011-rs2645339-rs762724 showed significance (P = 0.0239), but such association did not remain significant after multiple testing corrections. Conclusions Our data suggested that genetic variants in GRM6 are associated with high myopia. The mechanism of GRM6 in the development of high myopia need to be further investigated.

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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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The Associations between Single Nucleotide Polymorphisms of DNA Repair Genes, DNA Damage, and Age-Related Cataract: Jiangsu Eye Study

Cited by 37 publications

References 35 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

Association of ZNF644, GRM6, and CTNND2 genes with high myopia in the Han Chinese population: Jiangsu Eye Study

Molecular Genetics of Cataract

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