title: DNA methylation pattern of CALCA in preterm neonates with bacterial sepsis as a putative epigenetic biomarker.
abstract: Diagnosis of bacterial sepsis in preterm neonates can be difficult when using serum markers that rely on physiological changes because these changes may not necessarily be the result of bacterial infections alone. This retrospective investigation explores the potential use of the DNA methylation pattern of CpG sites in the promoter region of the calcitonin-related polypeptide α (CALCA) gene as an epigenetic biomarker for bacterial sepsis in preterm newborns. Four novel changes in the DNA methylation of eight CpG sites were detected in this gene and are present only in neonates with bacterial sepsis: (1) partial methylation at -769 CpG in gram-negative or gram-positive early onset sepsis (EOS) and late onset sepsis (LOS) episodes; (2) demethylation of 8 CpGs in gram-negative EOS followed by LOS (ELS) and in gram-negative EOS; (3) demethylation of 7 CpGs in gram-positive ELS and gram-positive EOS; (4) -771 C:G>T:A; 5' de novo -778 CpG mutation on both alleles in EOS. These changes were not detected in birth weight and gestational age matched controls or in newborns with isolated infections. Our results indicate that the DNA methylation pattern of the promoter region of the CALCA gene varies in different types of bacterial preterm sepsis, thus suggesting a potential use as an epigenetic biomarker. A prospective confirmation of these results is essential.
authors.affiliation: Department of Paediatrics and Adolescent Medicine; Medical University of Vienna; Vienna, Austria.
authors.forename: Kristina A
authors.initials: KA
authors.lastname: Tendl
authors.affiliation: Department of Paediatrics and Adolescent Medicine; Medical University of Vienna; Vienna, Austria.
authors.forename: Stefan M F
authors.initials: SM
authors.lastname: Schulz
authors.affiliation: Department of Paediatrics and Adolescent Medicine; Medical University of Vienna; Vienna, Austria.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Mechtler
authors.affiliation: Department of Paediatrics and Adolescent Medicine; Medical University of Vienna; Vienna, Austria.
authors.forename: Adele
authors.initials: A
authors.lastname: Bohn
authors.affiliation: Department of Paediatrics and Adolescent Medicine; Medical University of Vienna; Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Metz
authors.affiliation: Department of Paediatrics and Adolescent Medicine; Medical University of Vienna; Vienna, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Greber-Platzer
authors.affiliation: Department of Paediatrics and Adolescent Medicine; Medical University of Vienna; Vienna, Austria.
authors.forename: David C
authors.initials: DC
authors.lastname: Kasper
authors.affiliation: Department of Paediatrics and Adolescent Medicine; Medical University of Vienna; Vienna, Austria.
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Herkner
authors.affiliation: Department of Paediatrics and Adolescent Medicine; Medical University of Vienna; Vienna, Austria.
authors.forename: Chike B
authors.initials: CB
authors.lastname: Item
mesh_terms: D016470:Bacteremia / Q000175:diagnosis / Q000378:metabolism* / Q000382:microbiology; D015415:Biomarkers / Q000097:blood; D002116:Calcitonin / Q000235:genetics* / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000175:diagnosis / Q000378:metabolism* / Q000382:microbiology; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D018805:Sepsis / Q000175:diagnosis / Q000378:metabolism* / Q000382:microbiology
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide
keywords: CALCA; DNA-methylation; epigenetics; neonates; sepsis