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Matrix metalloproteinase (MMP)‐9 and VEGF gene interaction models and MMP‐9 plasma levels in preeclampsia and gestational hypertension
Author(s) -
Luizon Marcelo Rizzatti,
Sandrim Valeria C.,
Palei Ana Carolina T.,
Lacchini Riccardo,
Cavalli Ricardo C.,
Duarte Geraldo,
Tanus-Santos Jose Eduardo
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.848.3
Subject(s) - preeclampsia , haplotype , genotype , matrix metalloproteinase , gestational hypertension , medicine , allele , angiogenesis , pathophysiology , endocrinology , multifactor dimensionality reduction , epistasis , gene , biology , bioinformatics , pregnancy , genetics , single nucleotide polymorphism
Preeclampsia (PE) is a major contributor to maternal mortality worldwide but its etiology remains unclear. Although epistasis is suggested to be an important contributor to complex diseases, only a few studies have addressed this issue in PE. We detect interaction models predictive of PE (n=122) and gestational hypertension (GH, n=107) between polymorphisms in the promoter region of MMP‐9 (C‐1562T) and VEGF (G‐634C) genes using robust multifactor dimensionality reduction (RMDR) method. This best model of interaction included the ‐1562CT genotype and the ‐ 1562T allele was previously associated with increased MMP‐9 expression. However, previous findings showed no significant differences in plasma MMP‐9 levels in women with PE when single genotypes or MMP‐9 haplotypes were considered. Therefore, we investigate if gene‐gene interactions were associated with MMP‐9 levels in PE and GH. We observed only a marginally association finding (P=0.055) in GH. Indeed, the origin of plasma MMP‐9 levels is unknown, and it is possible that fetal MMP‐9 genotypes, tissue inhibitors of MMPs (TIMPs) and environmental factors may also contribute to the plasma MMP‐9 levels. We characterized interactions among genes related to angiogenesis and endothelial dysfunction seen in PE. Moreover, our study also provides further insights in the pathophysiology of PE and GH. Research support: CNPq, FAPESP and CAPES