Abstract
BackgroundA 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.MethodsCase–control study conducted at a tertiary hospital in São 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® 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 χ2 and Odds Ratio. Logistic regression was performed. Clinical and sociodemographic data were analyzed by Fisher’s exact test and Mann–Whitney.ResultsPTL 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).ConclusionThere 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.
Highlights
A genetic predisposition to Preterm Labor (PTL) and Preterm Premature Rupture of Membranes (PPROM) has been suggested; the relevance of polymorphisms and ancestry to susceptibility to PTL and PPROM in different populations remains unclear
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
Summary
A genetic predisposition to Preterm Labor (PTL) and Preterm Premature Rupture of Membranes (PPROM) has been suggested; the relevance of polymorphisms and ancestry to susceptibility to PTL and PPROM in different populations remains unclear. Spontaneous Preterm Labor (PTL) and Preterm Premature Rupture of Membranes (PPROM) are major contributors to neonatal mortality and serious neonatal morbidity worldwide [1]. Regardless of pathologic or physiologic status of labor, this process is always accompanied by a shift from anti-inflammatory to pro-inflammatory state which mediates the events of myometrial contractility, cervical ripening and rupture of fetal membranes that culminate in birth. Predictive biomarkers and effective prevention and treatment strategies are yet to be elucidated It seems clear, that a genetic predisposition can contribute to PTL and PPROM. The well documented discrepancy in the rates of these adverse outcomes among different ethnicities and populations [11,12,13] reinforces the importance of genetic and environmental variations in the susceptibility to develop PTL and PPROM
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