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.

Abstract:Introduction: Transforming growth factor beta 1 (TGFB1) and platelet-derived growth factor (PDGF) are the main cytokines related to hepatic fibrogenesis. Methods: RNA isolated from the platelets and hepatic tissue of 43 HCV carriers was used for quantitative polymerase chain reaction to determine TGFB1, PDGFA, and PDGFB RNA expression. Results: The mRNA expression of PDGFA in platelets was significantly lower in the group with advanced fibrosis than in the group with earlystage fibrosis. TGFB1 was more frequently expressed in platelets than in hepatic tissue, which was different from PDGFB. Conclusions: A pathway mediated by overexpression of TGFB1 via PDGFA in megakaryocytes could be involved in the development of fibrosis.Keywords: Hepatic fibrosis. PDGF. TGFB.Hepatic fibrosis, a consequence of various chronic stimuli, including infection with hepatitis C virus (HCV), is characterized by the progressive accumulation of extracellular matrix (ECM) components in the hepatic parenchyma, which leads to a progressive replacement of the functional tissue with scar tissue 1 .Hepatic stellate cells (HSCs) are considered the main cells producing ECM proteins 2 and their activation and proliferation are mediated by two cytokines, transforming growth factor beta 1 (TGFB1) and platelet-derived growth factor (PDGF). Both are secreted by HSCs, platelets, and other cells 3,4 .Transforming growth factor beta 1 is the major profibrogenic cytokine in the liver because of its contribution to fibrosis development via HSC activation and the regulation of gene expression associated with signaling cascades related to fibrosis 5,6 . Platelet-derived growth factor is the most potent mitogen for HSCs 7 . There are four different PDGF isoforms 8 and the PDGFB isoform is considered the most important mitogen for HSCs [7][8][9] . However, studies have demonstrated that PDGFA can also be considered an important profibrogenic agent, acting via TGFB1 induction 10 .Considering that platelets are major sources of TGFB1 and PDGF, which are growth factors involved in the development of liver fibrosis associated with chronic hepatitis C, and that studies have already demonstrated that platelets that accumulate in the liver during chronic hepatitis may be involved in hepatic fibrosis 11 , the aim of this study was to evaluate the expressions of PDGFA, PDGFB, and TGFB1 in hepatic tissue and platelets from HCV-infected patients presenting with varying degrees of hepatic fibrosis.Aliquots of ethylenediaminetetraacetic acid (EDTA)-anticoagulated peripheral venous blood and fragments of hepatic tissue were collected from 43 HCV-infected patients who presented at the Department of Internal Medicine, Gastroenterology Division, Botucatu Medical School, São Paulo State University [Universidade Estadual Paulista (UNESP)], Botucatu, SP, Brazil. The inclusion criteria were naïve patients infected with HCV genotype 1 who were aged >18 years, had undergone a liver biopsy before the start of antiviral treatment, and had signed informed consent. The exclu...

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The aim of this communication was to describe the detection of the coexistence of HIV-1 variant with dipeptide insertion between codons 69 and 70 of reverse transcriptase. These variants were isolated from a 16-year-old male patient, undergoing treatment in the city of Marilia, SP, Southeastern Brazil. After confi rmation of treatment failure, resistance to antiretroviral drugs testing was performed and two variants with the insertions of the aminoacids Ser-Gly/ Ser-Ala at codon 69 of reverse transcriptase were detected, besides the T69S mutation. These insertions have low prevalence, have not been reported in situations of coexistence in Brazil and are related to multidrug resistance, which makes this epidemiological fi nding relevant.