Genome-wide DNA hypermethylation and homocysteine increase a risk for myopia

作     者：Edward Hsi Yung-Song Wang Chia-Wei Huang Ming-Lung Yu Suh-Hang Hank Juo Chung-Ling Liang 

作者机构：Centre for Myopia and Eye DiseaseDepartment of Medical ResearchChina Medical University(Taiwan) Hospital Department of Genome MedicineKaohsiung Medical University Institute of Fisheries ScienceNational Taiwan University Department of BiotechnologyKaohsiung Medical University Hepatobiliary DivisionDepartment of Internal MedicineKaohsiung Medical University Hospital Faculty of MedicineCollege of Medicine Kaohsiung Medical University Centre for Myopia and Eye Disease Department of Medical ResearchChina Medical University(Taiwan) Hospital Graduate Institute of Biomedical SciencesChina Medical University(Taiwan) Institute of New Drug DevelopmentChina Medical University(Taiwan) Drug Development CenterChina Medical University(Taiwan) Department of OphthalmologyAsia University Hospital Department of OptometryCollege of Medical and Health ScienceAsia University 

出 版 物：《International Journal of Ophthalmology(English edition)》 (国际眼科杂志（英文版）)

年 卷 期：2019年第12卷第1期

页      面：38-45页

核心收录：

学科分类：10[医学] 

基　　金：Supported by the grants from the Taiwan Ministry of Science and Technology(MOST 104-2622-B-037-005) Taiwan Ministry of Health and Welfare Clinical Trial Centre(MOHW107-TDU-B-212-123004) Drug Development Center,China Medical University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education(MOE)in Taiwan 

主　　题：methylation myopia LINE-1 homocysteine dopamine 

摘      要：AIM: To test for the association between genome-wide methylation and myopia in human and mice. METHODS: Long interspersed nucleotide element 1(LINE-1) methylation levels were used to surrogate genome-wide methylation level. We first tested for the association between high myopia(-6 D) and LINE-1 methylation in leukocytes in 220 cases and 220 control subjects. Secondly, we validated the results of LINE-1 methylation in eyes from the form deprivation myopia(FDM) mice. Furthermore,we calculated the correlation of LINE-1 methylation levels between leukocyte DNA and ocular DNA in the mice. We also tested whether dopamine can alter LINE-1 methylation levels. RESULTS: The LINE-1 methylation level was significantly higher in the myopic human subjects than controls. The upper and middle tertiles of the methylation levels increased an approximately 2-fold(P≤0.002) risk for myopia than the lower tertile. Similarly, FDM mice had high LINE-1 methylation levels in the leukocyte, retina and sclera, and furthermore the methylation levels detected from these three tissues were significantly correlated. Immunohistochemical staining revealed higher levels of homocysteine and methionine in the rodent myopic eyes than normal eyes. Dopamine treatment to the cells reduced both LINE-1 methylation and DNA methyltransferase levels. CONCLUSION: LINE-1 hypermethylation may be associated with high myopia in human and mice. Homocysteine and methionine are accumulated in myopic eyes, which may provide excess methyl group for genome-wide methylation.