Ancestry informative markers and selected single nucleotide polymorphisms in immunoregulatory genes on preterm labor and preterm premature rupture of membranes: a case control study

Autor(es)

de Andrade Ramos, Bruna Ribeiro ^[1] ; Mendes, Niele Dias ^[1] ; Tanikawa, Aline Aki ^[2] ; Trindade Amador, Marcos Antonio ^[3] ; Carneiro dos Santos, Ney Pereira ^[3] ; Batista dos Santos, Sidney Emanuel ^[3] ; Castelli, Erick C. ^[1] ; Witkin, Steven S. ^[4] ; da Silva, Marcia Guimaraes ^[1]

Afiliação do(s) autor(es)

^[1] UNESP, Botucatu Med Sch, Dept Pathol, BR-18618970 Botucatu, SP - Brazil

^[2] UNESP, Botucatu Med Sch, Blood Transfus Ctr, BR-18618970 Botucatu, SP - Brazil

^[3] Fed Univ Para, Inst Biol Sci, Dept Genet, BR-66059 Belem, Para - Brazil

^[4] Weill Cornell Med Coll, Dept Obstet & Gynecol, New York, NY - USA

• Tipo de documento: Artigo Científico
• Fonte: BMC PREGNANCY AND CHILDBIRTH; v. 16, FEB 5 2016.
• Citações Web of Science: 8

Resumo

Background: A genetic predisposition to Preterm Labor (PTL) and Preterm Premature Rupture of Membranes (PPROM) has been suggested; however the relevance of polymorphisms and ancestry to susceptibility to PTL and PPROM in different populations remains unclear. The aim of this study was to evaluate the contribution of maternal and fetal SNPs in the IL1B, IL6, IL6R, TNFA, TNFR, IL10, TLR2, TLR4, MMP9, TIMP1 and TIMP2 genes and the influence of ancestry background in the susceptibility to PTL or PPROM in Brazilian women. Methods: Case-control study conducted at a tertiary hospital in Sao Paulo State, Brazil. We included women with PTL or PPROM and their babies (PTL: 136 women and 88 babies; PPROM: 65 women and 44 babies). Control group included 402 mother-babies pairs of term deliveries. Oral swabs were collected for identification of AIMs by fragment analysis and SNPs by Taqman (R) SNP Genotyping Assays and PCR. Linkage Disequilibrium and Hardy-Weinberg proportions were evaluated using Genepop 3.4. Haplotypes were inferred using the PHASE algorithm. Allele, genotype and haplotype frequencies were compared by Fisher's exact test or chi(2) and Odds Ratio. Logistic regression was performed. Clinical and sociodemographic data were analyzed by Fisher's exact test and Mann-Whitney. Results: PTL was associated with European ancestry and smoking while African ancestry was protective. The fetal alleles IL10-592C (rs800872) and IL10-819C (rs1800871) were also associated with PTL and the maternal haplotype TNFA-308G-238A was protective. Maternal presence of IL10-1082G (rs1800896) and TLR2A (rs4696480) alleles increased the risk for PPROM while TNFA-238A (rs361525) was protective. Family history of PTL/PPROM was higher in cases, and time to delivery was influenced by IL1B-31T (rs1143627) and TLR4-299G (rs4986790). Conclusion: There is an association between European ancestry and smoking and PTL in our Brazilian population sample. The presence of maternal or fetal alleles that modify the inflammatory response increase the susceptibility to PTL and PPROM. The family history of PTL/PPROM reinforces a role for genetic polymorphisms in susceptibility to these outcomes. (AU)

• Processo FAPESP: 11/19183-2 - Polimorfismos dos genes IL6 e IL6R candidatos à predisposição à rotura prematura de membranas pré-termo e ao trabalho de parto pré-termo
• Beneficiário: Niele Dias Mendes
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica