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

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

GABRIELA VÁZQUEZ-ARMENTA,¹ NATALIA GONZÁLEZ-LEAL,² MAYRA J VÁZQUEZ-DE LA TORRE,² JOSÉ FRANCISCO MUÑOZ-VALLE,³ MARTHA E RAMOS-MÁRQUEZ,³ IVÁN HERNÁNDEZ-CAÑAVERAL,⁴ ARTURO PLASCENCIA-HERNÁNDEZ² and FERNANDO SILLER-LÓPEZ^5,6

¹Doctorado en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México
²Servicio Infectología Pediátrica, Hospital Civil de Guadalajara “Fray Antonio Alcalde”, Universidad de Guadalajara, Guadalajara, Jalisco, México
³Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México

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.

keywords —— genetic polymorphism; heme oxygenase; inflammatory cytokines; oxidative stress; pediatric sepsis

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Tohoku J. Exp. Med., 2013, 231, 201-209

Correspondence: Fernando Siller-López, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada 950, Col. Independencia, Guadalajara, Jalisco 44340, México.

e-mail: fsiller@cucs.udg.mx