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Role of polymorphic variants as genetic modulators of infection in neonatal sepsis.

ABSTRACT: This study is a retrospective, case control study involving 535 preterm infants examining the roles of sequence polymorphisms in genes that mediate host immune responses to bacterial infection in newborn infants. A total of 49 single nucleotide polymorphisms (SNPs) in 19 candidate genes including inflammatory cytokines (IL6, IL10, IL1B, and TNF), cytokine receptors (IL1RN), toll-like receptors (TLR2, TLR4, and TLR5), and cell surface receptors (CD14) were genotyped. Subjects were stratified into three groups (sepsis, suspected sepsis, and control). The data were analyzed using a family-based transmission disequilibrium test. We found that birth weight, gestational age, duration of rupture of membranes, and presence of clinical chorioamnionitis were strongly associated with sepsis. Polymorphisms in TLR2 (rs3804099), TLR5 (rs5744105), IL10 (rs1800896), and PLA2G2A (rs1891320) genes were associated with sepsis. Allelic variants in PLA2G2A and TLR2 were associated with Gram-positive infections, whereas IL10 was associated with Gram-negative infections (p < 0.05). We conclude allelic variations in PLA2G2A, TLR2, TLR5, and IL10 may moderate the predisposition to sepsis in preterm infants.

SUBMITTER: Abu-Maziad A

PROVIDER: S-EPMC2940937 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Role of polymorphic variants as genetic modulators of infection in neonatal sepsis.

Abu-Maziad Asmaa A Schaa Kendra K Bell Edward F EF Dagle John M JM Cooper Margaret M Marazita Mary L ML Murray Jeffrey C JC

Pediatric research 20101001 4

This study is a retrospective, case control study involving 535 preterm infants examining the roles of sequence polymorphisms in genes that mediate host immune responses to bacterial infection in newborn infants. A total of 49 single nucleotide polymorphisms (SNPs) in 19 candidate genes including inflammatory cytokines (IL6, IL10, IL1B, and TNF), cytokine receptors (IL1RN), toll-like receptors (TLR2, TLR4, and TLR5), and cell surface receptors (CD14) were genotyped. Subjects were stratified into ...[more]

PMID: 20463618

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Project description:BackgroundProteomic analysis of amniotic fluid shows the presence of biomarkers characteristic of intrauterine inflammation. We sought to validate prospectively the clinical utility of one such proteomic profile, the Mass Restricted (MR) score.Methods and findingsWe enrolled 169 consecutive women with singleton pregnancies admitted with preterm labor or preterm premature rupture of membranes. All women had a clinically indicated amniocentesis to rule out intra-amniotic infection. A proteomic fingerprint (MR score) was generated from fresh samples of amniotic fluid using surface-enhanced laser desorption ionization (SELDI) mass spectrometry. Presence or absence of the biomarkers of the MR score was interpreted in relationship to the amniocentesis-to-delivery interval, placental inflammation, and early-onset neonatal sepsis for all neonates admitted to the Newborn Special Care Unit (n = 104). Women with "severe" amniotic fluid inflammation (MR score of 3 or 4) had shorter amniocentesis-to-delivery intervals than women with "no" (MR score of 0) inflammation or even "minimal" (MR score of 1 or 2) inflammation (median [range] MR 3-4: 0.4 d [0.0-49.6 d] versus MR 1-2: 3.8 d [0.0-151.2 d] versus MR 0: 17.0 d [0.1-94.3 d], p < 0.001). Nonetheless, a "minimal" degree of inflammation was also associated with preterm birth regardless of membrane status. There was a significant association between the MR score and severity of histological chorioamnionitis (r = 0.599, p < 0.001). Furthermore, neonatal hematological indices and early-onset sepsis significantly correlated with the MR score even after adjusting for gestational age at birth (OR for MR 3-4: 3.3 [95% CI, 1.1 to 9.2], p = 0.03). When compared with other laboratory tests routinely used to diagnose amniotic fluid inflammation and infection, the MR score had the highest accuracy to detect inflammation (white blood cell count > 100 cells/mm3), whereas the combination of Gram stain and MR score was best for rapid prediction of intra-amniotic infection (positive amniotic fluid culture).ConclusionsHigh MR scores are associated with preterm delivery, histological chorioamnionitis, and early-onset neonatal sepsis. In this study, proteomic analysis of amniotic fluid was shown to be the most accurate test for diagnosis of intra-amniotic inflammation, whereas addition of the MR score to the Gram stain provides the best combination of tests to rapidly predict infection.

Dataset Information

Role of polymorphic variants as genetic modulators of infection in neonatal sepsis.

Publications

Role of polymorphic variants as genetic modulators of infection in neonatal sepsis.

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