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Do patients with lupus and obesity have altered methylation profile of inflammatory-related genes? A cross-sectional study

Grant number: 21/09777-4
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): February 01, 2022
Effective date (End): March 31, 2024
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Carolina Nicoletti Ferreira Fino
Grantee:Lucas de Moura Carvalho
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:20/01893-2 - Progress in epigenetics on autoimmune rheumatic diseases: from basic studies to bedside in Lupus Erythematosus, Systemic, AP.JP
Associated scholarship(s):22/13317-1 - Folic acid treatment and IL-2 methylation levels in adipocytes from lupus´ patients: in vitro study, BE.EP.MS


Systemic lupus erythematosus (SLE) has been related to a series of highly complex imbalances, as they are attributed both to environmental factors and to genetic and epigenetic factors. Thus, a better understanding of these epigenetic alterations contributes to the adequate multidisciplinary management and treatment for the attenuation of the pathophysiology. Occasionally, it is known that the association of obesity and SLE is of an unknown nature, therefore, knowledge of the epigenetic alterations among these pathologies is scarce. The cross-sectional study aims to assess whether there is a specific and different epigenetic profile in obese and normal weight SLE patients and whether supplementation with folic acid and vitamin B12 is able to modulate epigenetic changes in the blood and adipose tissue of obese SLE patients and with normal weight. 48 premenopausal female patients, aged 18 to 40 years, with SLEDAI score d 4 on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), under glucocortoid treatment at a dose < 10 mg / d, and under treatment with chloroquine at a stable dose will be selected and submitted to a supplemental protocol of folic acid and vitamin B12 for 3 months. Patients will be evaluated before and after supplementation. Clinical parameters (duration of illness, current and cumulative dose of prednisone) will be evaluated through review of medical records and interviews with patients. Anthropometric assessment (weight, height, body mass index) and body composition (lean mass and fat mass), food intake assessment (by 24-hour food recalls) and biochemical assessment (glycemia, lipid profile, C-reactive protein, vitamin B12, folic acid, leptin, adiponectin and cytokines). For epigenetic analysis (DNA methylation, hydroxymethylation and microRNA) and gene expression, 2g of abdominal subcutaneous adipose tissue will be collected by biopsy in the same region above the patient's upper right umbilical scar. For DNA methylation analysis, a total of 4 ¼L of treated DNA will be used for hybridization on the Infinium Human Methylation EPIC Beadchip platform. Gene expression analysis will be performed in triplicate by qPCR using the 7500 Fast Real PCR System (Applied Biosystems). The target genes are: IL-2, IL-17A, STAT3, CREM2, DMNT1 and DMNT3. The expression of the following microRNAs will be evaluated: miR-21, miR-126, miR-132, miR-145, miR-146 and miR-181. In the statistical analysis, Shapiro-Wilk tests, independent t test, Mann-Whitney U test, repeated measures ANOVA and/or Wilcoxon tests will be used. Interactions will be inferred through linear regressions and Pearson or Spearman correlation. Data analysis will be performed using the Statistical Package for Social Science (SPSS version 22.0 Inc. Chicago. IL). The level of significance will be set at p d 0.05.

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