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Association between haplotypes of MMP-2 and MMP-9 and polycystic ovary syndrome: effects on plasma concentrations of MMP-2 and MMP-9.

Grant number: 12/04307-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): August 01, 2012
Effective date (End): July 31, 2015
Field of knowledge:Health Sciences - Medicine - Maternal and Child Health
Principal Investigator:Rui Alberto Ferriani
Grantee:Valeria Aguiar Gomes
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age and it is often associated with some cardiovascular risk factors such as obesity and resistance to insulin. As a result, it is believed that women with this syndrome can develop cardiovascular disease (CVD) earlier. Although there are no prospective studies which evaluated the mortality from cardiovascular disease in patients with the syndrome, some studies show changes in the endothelial function and elevation of inflammatory and biochemical markers of CVD in PCOS patients, and some of these findings are associated with the presence of subclinical atherosclerosis. The atherosclerosis is characterized by a remodeling of the extracellular matrix in which the metalloproteinases of the matrix (MMPs), especially MMP-2 and MMP-9, have been implicated as key mediators. The genes of MMP-2 and MMP-9 present functional polymorphisms which can modulate their expression and consequently their plasma concentrations. Some genetic studies show the association between the functional polymorphisms of the MMP-2 and MMP-9 genes and the presence and severity of cardiovascular diseases. However, no previous study has investigated the possible combination of the genetic polymorphisms isolated or combined in haplotypes of the MMP-2 and MMP-9 genes and their plasma concentrations in patients with PCOS. Thus, the aim of this project is to evaluate the effects of the MMP-2 and MMP-9 polymorphisms in women with PCOS. We intend to study 100 women diagnosed with PCOS and 100 control patients. We will also evaluate the plasma concentration of MMP-2 and MMP-9 ELISA and we will genotyped the genetic polymorphisms of MMP-2 (C-1306T and C-735T), MMP-9 (-90 (CA) n, C-1562T and Q279R). PHASE software will be used to determine the haplotypes (combinations of the genetic polymorphisms in the same gene). The genotypes and alleles of the MMP-2 and MMP-9 polymorphism as well as their combination haplotypes will be evaluated for the association with PCOS and plasma levels of the respective enzymes MMP-2 and MMP-9.