title: Short (GT)n microsatellite repeats in the heme oxygenase-1 gene promoter are associated with antioxidant and anti-inflammatory status in Mexican pediatric patients with sepsis.
abstract: An adequate immune and antioxidant response is a key to the resolution of sepsis. Heme oxygenase-1 (HMOX1) is a stress protein with a polymorphic (GT)n repeat in its gene promoter that regulates its expression in response to oxidative injury, such as that present in sepsis. HMOX1 is the rate-limiting enzyme of heme degradation, and the heme breakdown products, CO, Fe, and bilirubin, are considered to be biologically active metabolites with direct or indirect antioxidant and anti-inflammatory properties. In this study, we investigated the inflammatory and antioxidant response and the relationship with the HMOX1 levels and HMOX1 polymorphism in Mexican septic pediatric patients. In a case-control pilot study, we enrolled 64 septic patients and 72 hospitalized control patients without a diagnosis of sepsis. DNA extracted from buffy coat was genotyped for HMOX1 (GT)n polymorphism by PCR and markers of antioxidant and inflammatory status were quantified in plasma by analysis of the oxygen radical absorbance capacity (ORAC), protein carbonyl (PC), interleukin (IL) 6, IL10, and HMOX1 levels. In septic children, oxidative and inflammatory markers were elevated, and HMOX1 levels were positively correlated with IL10 levels. Genotypic and allelic distribution of HMOX1 polymorphism showed no difference between groups. HMOX1 short-allele septic carriers (< 25 GT repeats) presented favorable ORAC, PC and IL10 levels. This study confirms that an active response against pediatric sepsis involves the expression of HMOX1 and IL10, suggesting that the high antioxidant status associated with HMOX1 short-allele septic carriers might provide a beneficial environment for sepsis resolution.
authors.affiliation: Doctorado en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Vázquez-Armenta
authors.forename: Natalia
authors.initials: N
authors.lastname: González-Leal
authors.forename: Mayra
authors.initials: M
authors.lastname: J Vázquez-de la Torre
authors.forename: José Francisco
authors.initials: JF
authors.lastname: Muñoz-Valle
authors.forename: Martha E
authors.initials: ME
authors.lastname: Ramos-Márquez
authors.forename: Iván
authors.initials: I
authors.lastname: Hernández-Cañaveral
authors.forename: Arturo
authors.initials: A
authors.lastname: Plascencia-Hernández
authors.forename: Fernando
authors.initials: F
authors.lastname: Siller-López
mesh_terms: D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood; D003710:Demography; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008800:Mexico; D018895:Microsatellite Repeats / Q000235:genetics*; D010084:Oxidation-Reduction; D011401:Promoter Regions, Genetic; D018805:Sepsis / Q000097:blood / Q000201:enzymology / Q000235:genetics* / Q000382:microbiology; D018709:Statistics, Nonparametric
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D016207:Cytokines; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1