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

Grant number: 11/08083-7
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2012
Effective date (End): April 30, 2015
Field of knowledge:Health Sciences - Medicine - Maternal and Child Health
Principal Investigator:Márcia Guimarães da Silva
Grantee:Bruna Ribeiro de Andrade Ramos
Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Backgroud: Preterm Labor (PL) is an ongoing problem that complicates approximately 10% of pregnancies worldwide, being the major contributor to perinatal morbidity and mortality. Around 30% of PL are due to Preterm Premature Rupture of Membranes (PPROM) and in that cases, morbidity may be even further increased. 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 remains 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 DNA variants in maternal and fetal genomes in the 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 (UFPA). 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.

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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; 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, . (11/08083-7, 11/09433-1)
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, . (11/09433-1, 11/08083-7)
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, v. 34, n. 22, p. 3684-3689, . (11/09433-1, 11/08083-7)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
RAMOS, Bruna Ribeiro de Andrade. Polimorfismos de genes pró e anti-inflamatórios candidatos à predisposição à rotura prematura de membranas pré-termo e ao trabalho de parto pré-termo. 2015. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Faculdade de Medicina. Botucatu Botucatu.

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