# Literary Identification of Differentially Hydroxymethylated DNA Regions for Type 2 Diabetes Mellitus: A Scoping Minireview

## TL;DR

This review identifies blood DNA regions with altered hydroxymethylation in Type 2 Diabetes, focusing on the SOCS3 gene and its potential role in disease development.

## Contribution

The study is the first to systematically identify differentially hydroxymethylated DNA regions in T2DM using a scoping review approach.

## Key findings

- Global 5hmC levels are higher in T2DM patients compared to healthy controls in blood cells.
- The SOCS3 gene shows increased hydroxymethylation in T2DM patients with high poly-ADP-ribosylation.
- Only three case-control studies met the criteria for full-text review, highlighting limited research in this area.

## Abstract

Type 2 diabetes mellitus (T2DM) is a public health condition where environmental and genetic factors can intersect through hydroxymethylation. It was unclear which blood DNA regions were hydroxymethylated in human T2DM development. We aimed to identify the regions from the literature as designed in the ongoing Twins Discordant for Incident T2DM Study. A scoping review was performed using Medical Subject Headings (MeSH) and keyword methods to search PubMed for studies published in English and before 1 August 2022, following our registered protocol. The keyword and MeSH methods identified 12 and 3 records separately, and the keyword-identified records included all from the MeSH. Only three case-control studies met the criteria for the full-text review, including one MeSH-identified record. Increased global levels of 5-hydroxymethylated cytosine (5hmC) in T2DM patients versus healthy controls in blood or peripheral blood mononuclear cells were consistently reported (p < 0.05 for all). Among candidate DNA regions related to the human SOCS3, SREBF1, and TXNIP genes, only the SOCS3 gene yielded higher 5hmC levels in T2DM patients with high poly-ADP-ribosylation than participants combined from those with low PARylation and healthy controls (p < 0.05). Hydroxymethylation in the SOCS3-related region of blood DNA is promising to investigate for its mediation in the influences of environment on incident T2DM.