# Methylation of LINE-1 Retroelement in People with Type 1 Diabetes

## TL;DR

People with type 1 diabetes have higher LINE-1 methylation compared to healthy individuals, with specific patterns linked to disease markers like blood sugar levels and age of diagnosis.

## Contribution

This study is the first to report LINE-1 methylation patterns in people with type 1 diabetes and their associations with glycemic control and disease progression.

## Key findings

- PwT1D showed higher total LINE-1 methylation compared to healthy controls.
- The partial LINE-1 methylation pattern (uCmC) was less common in PwT1D and correlated with worse glycemic control and disease duration.
- Age at diagnosis of T1D was negatively associated with the uCmC methylation pattern.

## Abstract

Introduction: Emerging research indicates that alterations in the methylation of retrotransposons may contribute to genomic instability and cellular aging in various autoimmune disorders and diabetes mellitus (DM). As relevant information for people with type 1 diabetes mellitus (PwT1D) is limited, we aimed to investigate long interspersed nuclear element-1 (LINE-1) methylation status in this population. Methods: DNA methylation levels and patterns of LINE-1 were examined in the peripheral blood of 35 PwT1D and 28 healthy controls (age- and sex-matched), by using the COmbined Bisulfite Restriction Analysis methodology (COBRA). Results: Total LINE-1 methylation rate (mC) was higher in PwT1D compared to controls [47.3% (46.6–47.8%) vs. 46.5% (44.7–47.3%), p < 0.05]. The partial LINE-1 methylation pattern (uCmC) was less frequently observed in patients vs. controls [28.4% (24.7–33.3%) vs. 33.1% (27.8–37.9%), p < 0.05]. Prevalence of other methylation patterns [partially methylated (mCuC), hypermethylated (mCmC) and hypomethylated (uCuC)] was similar in the two groups. Furthermore, levels of fasting glucose and glycated hemoglobin (HbA1c) were positively associated with total methylation (mC) [Spearman’s rho = 0.380, p = 0.002 and rho = 0.342, p = 0.006, respectively], but negatively associated with the partially methylated (uCmC) pattern [Spearman’s rho = −0.383, p = 0.002 and rho = −0.270, p = 0.033, respectively]. The LINE-1 (uCmC) methylation pattern was negatively associated with the age at diagnosis of T1D [Spearman’s rho = −0.341, p = 0.049], but positively associated with disease duration [Spearman’s rho = 0.388, p = 0.021]. Conclusions: PwT1D were found to have higher total LINE-1 methylation rate (mC) compared to healthy controls. The partial methylation pattern (uCmC) was less frequently observed in these patients and was negatively associated with the glycemic status and the age at diagnosis of T1D, while demonstrating a positive correlation with disease duration.