title: 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.
authors.affiliation: Department of Pediatrics, University of Iowa, Children's Hospital, Iowa City, Iowa 52242, USA.
authors.forename: Asmaa
authors.initials: A
authors.lastname: Abu-Maziad
authors.forename: Kendra
authors.initials: K
authors.lastname: Schaa
authors.forename: Edward F
authors.initials: EF
authors.lastname: Bell
authors.forename: John M
authors.initials: JM
authors.lastname: Dagle
authors.forename: Margaret
authors.initials: M
authors.lastname: Cooper
authors.forename: Mary L
authors.initials: ML
authors.lastname: Marazita
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Murray
mesh_terms: D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005865:Gestational Age; D054501:Group II Phospholipases A2 / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D016753:Interleukin-10 / Q000235:genetics; D007484:Iowa; D016015:Logistic Models; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D018805:Sepsis / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051198:Toll-Like Receptor 5 / Q000235:genetics
chemical_list: C508609:IL10 protein, human; C495342:TLR2 protein, human; C495346:TLR5 protein, human; D051195:Toll-Like Receptor 2; D051198:Toll-Like Receptor 5; D016753:Interleukin-10; D054501:Group II Phospholipases A2; C516287:PLA2G2A protein, human
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