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Abstract：
OBJECTIVE: To identify the differential methylation sites (DMS) and their according genes associated with diabetic retinopathy (DR) development in type 1 diabetes (T1DM) children.
METHODS: This study consists of two surveys. A total of 40 T1DM children was included in the first survey. Because no participant has DR, retina thinning was used as a surrogate indicator for DR. The lowest 25% participants with the thinnest macular retinal thickness were included into the case group, and the others were controls. The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay, and compared between the case and control groups. Four DMS with a potential role in diabetes were identified. The second survey included 27 T1DM children, among which four had DR. The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing.
RESULTS: In the first survey, the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls (|Δβ|>0.1 and Adj.P<0.05), and 328 of these were identified with a significance of Adj.P<0.01. Among these, 319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls. Pyrosequencing revealed that the transcription elongation regulator 1 like (TCERG1L, cg07684215) gene was hypermethylated in the four T1DM children with DR (P=0.018), which was consistent with the result from the first survey. The methylation status of the other three DMS (cg26389052, cg25192647, and cg05413694) showed no difference (all P>0.05) between participants with and without DR.
CONCLUSIONS: The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.
METHODS: This study consists of two surveys. A total of 40 T1DM children was included in the first survey. Because no participant has DR, retina thinning was used as a surrogate indicator for DR. The lowest 25% participants with the thinnest macular retinal thickness were included into the case group, and the others were controls. The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay, and compared between the case and control groups. Four DMS with a potential role in diabetes were identified. The second survey included 27 T1DM children, among which four had DR. The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing.
RESULTS: In the first survey, the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls (|Δβ|>0.1 and Adj.P<0.05), and 328 of these were identified with a significance of Adj.P<0.01. Among these, 319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls. Pyrosequencing revealed that the transcription elongation regulator 1 like (TCERG1L, cg07684215) gene was hypermethylated in the four T1DM children with DR (P=0.018), which was consistent with the result from the first survey. The methylation status of the other three DMS (cg26389052, cg25192647, and cg05413694) showed no difference (all P>0.05) between participants with and without DR.
CONCLUSIONS: The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.
摘要：
目的：确定1型糖尿病（T1DM）儿童中与糖尿病视网膜病变（DR）发展相关的差异甲基化位点（DMS）及其相应基因。
方法：本研究包括两项调查。共有40名T1DM儿童被纳入第一次调查。因为没有参与者有DR，视网膜变薄被用作DR的替代指标。黄斑区视网膜厚度最低的25%参与者被纳入病例组，其他人是控制者.通过Illumina甲基化850K阵列BeadChip测定评估DNA甲基化状态，并对病例组和对照组进行比较。确定了四种在糖尿病中具有潜在作用的DMS。第二项调查包括27名T1DM儿童，其中四个有DR。通过焦磷酸测序在有和没有DR的参与者之间比较了由850K鉴定的四个DMS的甲基化模式。
结果：在第一次调查中，与对照组相比，850K阵列在病例组中显示出751个显着和差异甲基化的位点（|Δβ|>0.1和Adj。P<0.05),其中328个被确定为具有Adj的意义。P<0.01。其中,相对于对照组，病例组中319个CpG位点被高甲基化，432个CpG位点被低甲基化。焦磷酸测序揭示了转录延伸调节因子1样（TCERG1L，cg07684215)基因在4例T1DM合并DR患儿中呈高甲基化(P=0.018),这与第一次调查的结果一致。其他三个DMS（cg26389052，cg25192647和cg05413694）的甲基化状态在有和没有DR的参与者之间没有差异（均P>0.05）。
结论：TCERG1L基因的高甲基化是中国T1DM儿童发生DR的危险因素。
方法：本研究包括两项调查。共有40名T1DM儿童被纳入第一次调查。因为没有参与者有DR，视网膜变薄被用作DR的替代指标。黄斑区视网膜厚度最低的25%参与者被纳入病例组，其他人是控制者.通过Illumina甲基化850K阵列BeadChip测定评估DNA甲基化状态，并对病例组和对照组进行比较。确定了四种在糖尿病中具有潜在作用的DMS。第二项调查包括27名T1DM儿童，其中四个有DR。通过焦磷酸测序在有和没有DR的参与者之间比较了由850K鉴定的四个DMS的甲基化模式。
结果：在第一次调查中，与对照组相比，850K阵列在病例组中显示出751个显着和差异甲基化的位点（|Δβ|>0.1和Adj。P<0.05),其中328个被确定为具有Adj的意义。P<0.01。其中,相对于对照组，病例组中319个CpG位点被高甲基化，432个CpG位点被低甲基化。焦磷酸测序揭示了转录延伸调节因子1样（TCERG1L，cg07684215)基因在4例T1DM合并DR患儿中呈高甲基化(P=0.018),这与第一次调查的结果一致。其他三个DMS（cg26389052，cg25192647和cg05413694）的甲基化状态在有和没有DR的参与者之间没有差异（均P>0.05）。
结论：TCERG1L基因的高甲基化是中国T1DM儿童发生DR的危险因素。
