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

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

doi:10.18240/ijo.2019.01.06

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

Int J Ophthalmol. 2019 Jan 18;12(1):38-45. doi: 10.18240/ijo.2019.01.06. eCollection 2019.

Authors

Edward Hsi^{1

2}, Yung-Song Wang^{2

3}, Chia-Wei Huang⁴, Ming-Lung Yu^{5

6}, Suh-Hang Hank Juo^{1

7

8

9}, Chung-Ling Liang^{10

11}

Affiliations

¹ Centre for Myopia and Eye Disease, Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan.
² Department of Genome Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
³ Institute of Fisheries Science, National Taiwan University, Taipei 106, Taiwan.
⁴ Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
⁵ Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
⁶ Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
⁷ Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan.
⁸ Institute of New Drug Development, China Medical University, 91 Hsueh-Shih Road, Taichung 404, Taiwan.
⁹ Drug Development Center, China Medical University 404, Taiwan.
¹⁰ Department of Ophthalmology, Asia University Hospital, Taichung 413, Taiwan.
¹¹ Department of Optometry, College of Medical and Health Science, Asia University, Taichung 413, Taiwan.

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.

Keywords: LINE-1; dopamine; homocysteine; methylation; myopia.