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Polymorphisms in immunoregulatory genes and the risk of preterm premature rupture of membranes and preterm labor.

Grant number: 11/09433-1
Support type:Regular Research Grants
Duration: September 01, 2011 - February 28, 2014
Field of knowledge:Health Sciences - Medicine - Maternal and Child Health
Principal Investigator:Márcia Guimarães da Silva
Grantee:Márcia Guimarães da Silva
Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Assoc. researchers: Sidney Emanuel Batista dos Santos ; Steven Sol Witkin


Preterm Labor (PL) and Preterm Premature Rupture of Membranes (PPROM) are major contributors to perinatal morbidity and mortality. These complications have been described as inflammatory conditions and, as such, are deeply influenced by the production of cytokines and other inflammatory mediators. A genetic predisposition to PL and PPROM has been suggested, especially for genetic variation within immunoregulatory genes. However, the association between PL and PPROM and polymorphic genes is still not clear. The better understanding of genetic mechanisms underlying these complications would allow the identification of high-risk patients, minimizing the deleterious effects of prematurity. Objective: The objective of this study is to evaluate the association between polymorphisms in maternal and fetal genes IL1B, IL1RN, IL6, IL6R TNFA, TNFR, IL10, TLR2, TLR4, MMP1, MMP2, MMP9, TIMP1 and TIMP2 genes and increased risk for PL and PPROM. Study Design: This case-control study will include patients with history of PL and/or PPROM that delivered prematurely at the Obstetrical Unit Care of Botucatu Medical School, UNESP between 2004 and 2010. The control group will include patients with term pregnancies, matched to the case group by age, ethnicity, and sex of the newborn. Oral swabs (Cath-AllTM - Epicentre Biotechnologies) and saliva samples (Oralgene® - DNA Genotek) will be collected from all patients and respective children enrolled in this study. Ethnicity stratification will be performed using a multiplex assay standardized for Brazilian population at the Laboratory of Human and Medical Genetics, from Pará Federal University. After a training at Weill Cornell Medical College, New York, USA, genotyping of polymorphic genes will be performed at Department of Pathology, Botucatu Medical School, UNESP. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DE ANDRADE RAMOS, BRUNA RIBEIRO; COSI BENTO, GIOVANA FERNANDA; NAVASCUES BERNARDINO, ROMULO AUGUSTO; MIOT, HELIO AMANTE; SILVA, MARCIA GUIMARAES. Influence of single nucleotide polymorphisms (SNPs) in immunoregulatory genes in the morbidity of preterm newborns. Journal of Maternal-Fetal & Neonatal Medicine, NOV 2019. Web of Science Citations: 0.
DE ANDRADE RAMOS, BRUNA RIBEIRO; BARBIERI D'ELIA, MARIA PAULA; TRINDADE AMADOR, MARCOS ANTONIO; CARNEIRO SANTOS, NEY PEREIRA; BATISTA SANTOS, SIDNEY EMANUEL; CASTELLI, ERICK DA CRUZ; WITKIN, STEVEN S.; MIOT, HELIO AMANTE; BARTOLI MIOT, LUCIANE DONIDA; DA SILVA, MARCIA GUIMARAES. Neither self-reported ethnicity nor declared family origin are reliable indicators of genomic ancestry. Genetica, v. 144, n. 3, p. 259-265, JUN 2016. Web of Science Citations: 18.

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