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

Suh-Hang Hank Juo. China Medical University, Taichung, 91 Hsueh-Shih Road, Taichung 404, Taiwan. hjuo@mail.cmu.edu.tw; Chung-Ling Liang. Asian University Hospital, Department of Ophthalmology, 500 Lioufeng Road, Taichung City 41354, Taiwan. ling0228@gmail.com

Affiliation:

Clc Number:

Fund Project:

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) and 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.

  • Article
  • |
  • Figures
  • |
  • Metrics
  • |
  • Reference
  • |
  • Related
  • |
  • Cited by
  • |
  • Materials
  • |
  • Comments
    Abstract:

    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.

    Reference
    Related
    Cited by
Get Citation

Edward Hsi, Yung-Song Wang, Chia-Wei Huang, et al. Genome-wide DNA hypermethylation and homocysteine increase a risk for myopia. Int J Ophthalmol, 2019,12(1):38-45

Copy
Share
Article Metrics
  • Abstract:
  • PDF:
  • HTML:
  • Cited by:
Publication History
  • Received:May 25,2018
  • Revised:November 27,2018
  • Adopted:
  • Online: January 03,2019
  • Published: