DNA Methylation profile of patients with systemic lupus erythematosus and normal weight or excess body weight: an exploratory study

Author(s)

Lucas de Moura Carvalho

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
• Defense date: 2024-07-12

Examining board members

Carolina Nicoletti Ferreira Fino; Fabiana Braga Benatti; Maria Aderuza Horst; Carla Barbosa Nonino

• Advisor: Carolina Nicoletti Ferreira Fino

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease whose pathophysiology involves the interaction of environmental, hormonal, genetic, and epigenetic factors. Studies have revealed a profile of DNA hypomethylation in SLE patients, especially in cells and pathways related to immune system. The literature suggests that excess body weight in these patients may lead to increased disease activity, worsening quality of life, and elevated risk of cardiovascular diseases. Despite the known modulation of DNA methylation profiles by overweight and obesity, studies on epigenetic modifications in the context of SLE and excess body weight remain scarce. Therefore, this cross-sectional and exploratory study aimed to assess whether there is a specific epigenetic profile in SLE patients with excess weight or normal weight. Fifty-one premenopausal female patients, aged 18 to 45 years, with controlled disease activity, under treatment with prednisone with dose <10 mg/day, and stable chloroquine dose, were enrolled. Patients were divided into two groups based on body mass index (BMI): the normal weight group consisting of 23 patients with BMI between 18.5 and 24.9 kg/m², and the excess weight group consisting of 28 patients with BMI >25 kg/m². Sociodemographic, clinical, biochemical, hematological, immunological, and inflammatory parameters were evaluated. For DNA methylation and gene expression analysis, samples of abdominal subcutaneous adipose tissue were collected by biopsy. DNA methylation analysis was performed using the Infinium Human Methylation EPIC Beadchip assay (Illumina), considering changes in methylation levels of each CpG with a minimum value of 5%, p <0.001, and false discovery rate <0.05. Gene expression analysis of target genes was performed by polymerase chain reaction, using the 2Ct method. The excess weight group showed higher BMI, percentage of body fat, total cholesterol fractions, and lymphocyte percentage compared to the normal weight group. Conversely, serum concentrations of folic acid were lower in the excess weight group. A total of 28,577 CpG sites were differentially methylated between the groups (36.6% in the promoter region). Of these, 3,730 CpG sites were hypomethylated in patients with excess weight and were associated with the autoimmunity and cytokine-receptor interaction pathway. On the other hand, 3,342 CpG sites were hypermethylated in patients of the excess weight group and were related to the metabolism and degradation of fatty acids. Also, higher levels of DNMT1, TNF-, IL-6, LEP, and ADIPOQ expression were observed in patients of the excess weight group. Patients with SLE and excess body weight show a unique epigenetic signature than patients with normal weight, which may be related to disease´s clinical manifestation (AU)

• FAPESP's process: 21/09777-4 - Do patients with lupus and obesity have altered methylation profile of inflammatory-related genes? A cross-sectional study
• Grantee: Lucas de Moura Carvalho
• Support Opportunities: Scholarships in Brazil - Master