Hyper-Methylation of CpG Island in 5′ UTR of the HLA-G Gene Reduces Its Expression in Individuals with Immune Thrombocytopenia

Abstract

This study investigated the impact of DNA methylation in the 5′ untranslated region-CpG island (5′ UTR) of the HLA-G gene on soluble HLA-G (sHLA-G) levels in immune thrombocytopenia (ITP) patients, shedding light on sHLA-G’s regulatory mechanisms in ITP. Using a cohort of 53 participants, including ITP patients, DNA methylation profiles in the HLA-G gene’s 5′ UTR were analyzed with Sequenom MassARRAY Methylation Analysis. sHLA-G levels were measured by enzyme-linked immunosorbent assay, and platelet antibodies were assessed using modified MAIPA. Results showed increased DNA methylation at specific CpG sites (CpG3, CpG18, CpG19, and CpG20.21) in ITP patients. A negative correlation between DNA methylation and sHLA-G expression, particularly at CpG18, was found. Patients with Anti-GPIb/IX antibodies had higher CpG18 methylation. Age and gender didn’t correlate significantly with methylation. This underscores 5′ UTR hypermethylation’s role in influencing circulating HLA-G levels, revealing insights into ITP development and potential therapeutic targets. By linking DNA methylation to sHLA-G expression, this advances ITP understanding, suggesting new therapeutic strategies.