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Epigenetics markers assessment in women in pre and post menopause with altered glycemic profile

Grant number: 12/01742-8
Support type:Regular Research Grants
Duration: May 01, 2012 - October 31, 2014
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Paula Helena Ortiz Lima
Grantee:Paula Helena Ortiz Lima
Home Institution: Instituto Dante Pazzanese de Cardiologia (IDPC). Fundação Adib Jatene (FAJ). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Assoc. researchers:Marcelo Chiara Bertolami ; Mario Hiroyuki Hirata

Abstract

Androgens and estradiol (E2) are associated with diabetes mellitus and glucose intolerance. High levels of testosterone (T) free or bioavailability represent predictive factors for insulin resistance and Type 2 diabetes mellitus (T2DM) in women. Moreover, women with low levels of sex hormone binding globulin (SHBG) are also susceptible to developing type 2 diabetes. The Epigenetics has been described as heritable changes in function of a gene that occur without change in sequence of nucleotides of DNA. These epigenetic changes are potentially reversible and modulated by environmental, dietary or pharmacological intervention. Thus, can mediate changes in gene expression and genomic stability making them potentially important pathogenic mechanisms in complex multifactorial diseases such as T2DM. Therefore, the aim of this study is to evaluate the presence of epigenetic markers in pre-and postmenopausal women with clinical pre-diabetes or type 2 diabetes. Will be assessed 132 women screened at the Institute Dante Pazzanese of Cardiology (IDPC), aged 45-65 years. The patients are divided into four (4) groups: 1 - in normoglycemic premenopausal women, 2 - normoglycemic postmenopausal women, 3 - women with abnormal glucose profile (pre-diabetes) in premenopausal and 4 - postmenopausal women with T2DM. We will analyze anthropometric data such as height, blood pressure and BMI, and issues related to the habits and lifestyle. Will be evaluated biochemical parameters such as total cholesterol, HDL, triglycerides, glycated hemoglobin, fasting glucose, apo A and apo B, urea, creatinine, AST, ALT, T4, TSH, hsCRP, insulin, estradiol, progesterone, SHBG, well as TNF-alpha, adiponectin and leptin. Furthermore, will be evaluated: DNA methylation in promoter regions of genes SHBG, LDLR, HDLBP, ESR1, ESRRA, ESR2, EPR, INSR, TRAF5, COX-2, NFkB1, TNFRSF11A; the expression of miRNAs miR-150, miR- 124, miR-146th, miR-29a, miR-30d, miR-34a, miR-375, miR-9, miR-133a, miR-208th, miR-1, miR-133a, miR-208th, miR-423- 5p, miR-499-5p in plasma; acetylation in histones H3Ac, H4AC, H3K9ac in PBMC-cells monomorphonuclear peripheral blood of patients. The results of this study may contribute to the knowledge of some molecular mechanisms may be involved in the pathophysiology of diabetes and its complications. (AU)