We also compared our results to other methylation studies in myopia. Previously, the decrease in DNA methylation was linked to a higher risk of early-onset myopia.
31 Several CG dinucleotides identified as hypomethylated in umbilical cords of 29 myopic children of Chinese, Malay, or Indian origin from Singapore (with myopia diagnosed later at the age of 3 years), when compared to 490 matched controls in Seow et al.,
31 were not located in promoter regions and did not reach significant differences in methylation level in our study. In a study on chicks, the ocular growth development was not associated with substantial changes in DNA methylation, but significant changes in methylation levels at single CpG sites were found in the studied
EGR1,
FOS, and
NAB2 genes.
35 This supports our findings as we observed significant changes at individual CG sites, rather than the large-scale shifts, although at different genes. In another study, six CG dinucleotides in the promoter and exon 1 region of
Col1a1 were hypermethylated, and scleral
Col1a1 messenger RNA levels were reduced in the treated mouse eyes with monocular form-deprivation myopia (FDM) compared with normal murine control eyes,
32 suggesting that DNA methylation of the
Col1a1 promoter/exon 1 may inhibit the synthesis of scleral collagen leading to myopia development.
32 Although the
COL1A1 gene has been studied frequently as a candidate gene for HM, the outcomes are still inconsistent.
82–88 Significantly lower methylation of four CG sites in the
IGF1 gene promoter and moderately higher transcription level in the sclera were indicated in a guinea pig model of FDM, which suggest the role of this gene methylation in FDM pathogenesis.
34 We observed only nonsignificant changes in methylation levels of CG dinucleotides within this gene.