Promoter methylation status of RORC, IL17A, and TNFA in peripheral blood leukocytes in adolescents with obesity-related asthma
José J. Leija-Martínez,
Abraham Giacoman-Martínez,
Blanca E. Del-Río-Navarro,
Fausto Sanchéz-Muñoz,
Adrián Hernández-Diazcouder,
Onofre Muñoz-Hernández,
Rodrigo Romero-Nava,
Santiago Villafaña,
Laurence A. Marchat,
Enrique Hong,
Fengyang Huang
Affiliations
José J. Leija-Martínez
Universidad Nacional Autónoma de México, Programa de Maestría y Doctorado en Ciencias Médicas, Odontológicas y de la Salud, Mexico City, Mexico; Hospital Infantil de Mexico Federico Gómez, Research Laboratory of Pharmacology, Mexico City, Mexico
Abraham Giacoman-Martínez
Hospital Infantil de Mexico Federico Gómez, Research Laboratory of Pharmacology, Mexico City, Mexico; Department of Pharmacobiology, Centro de Investigacion de Estudio Avanzados del Instituto Politecnico Nacional, Calz. de Los Tenorios 235, Col. Granjas Coapa, Mexico City 14330, Mexico
Blanca E. Del-Río-Navarro
Universidad Nacional Autónoma de México, Programa de Maestría y Doctorado en Ciencias Médicas, Odontológicas y de la Salud, Mexico City, Mexico; Hospital Infantil de México Federico Gómez, Department of Pediatric Allergy-Clinical Immunology, Mexico City, Mexico
Fausto Sanchéz-Muñoz
Universidad Nacional Autónoma de México, Programa de Maestría y Doctorado en Ciencias Médicas, Odontológicas y de la Salud, Mexico City, Mexico; Departamento de Inmunología, Instituto Nacional de Cardiología “Ignacio Chávez”, Mexico City, Mexico
Adrián Hernández-Diazcouder
Departamento de Inmunología, Instituto Nacional de Cardiología “Ignacio Chávez”, Mexico City, Mexico
Onofre Muñoz-Hernández
Universidad Nacional Autónoma de México, Programa de Maestría y Doctorado en Ciencias Médicas, Odontológicas y de la Salud, Mexico City, Mexico
Rodrigo Romero-Nava
Hospital Infantil de Mexico Federico Gómez, Research Laboratory of Pharmacology, Mexico City, Mexico; Laboratorio de Señalización Intracelular, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico
Santiago Villafaña
Laboratorio de Señalización Intracelular, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico
Laurence A. Marchat
Laboratorio 2 de Biomedicina Molecular, ENMH, Instituto Politécnico Nacional, Mexico
Enrique Hong
Universidad Nacional Autónoma de México, Programa de Maestría y Doctorado en Ciencias Médicas, Odontológicas y de la Salud, Mexico City, Mexico; Department of Pharmacobiology, Centro de Investigacion de Estudio Avanzados del Instituto Politecnico Nacional, Calz. de Los Tenorios 235, Col. Granjas Coapa, Mexico City 14330, Mexico
Fengyang Huang
Universidad Nacional Autónoma de México, Programa de Maestría y Doctorado en Ciencias Médicas, Odontológicas y de la Salud, Mexico City, Mexico; Hospital Infantil de Mexico Federico Gómez, Research Laboratory of Pharmacology, Mexico City, Mexico; Corresponding author.
A higher Th17-immune response characterises obesity and obesity-related asthma phenotype. Nevertheless, obesity-related asthma has a more significant Th17-immune response than obesity alone. Retinoid-related orphan receptor C (RORC) is the essential transcription factor for Th17 polarisation. Previous studies have found that adolescents with obesity-related asthma presented upregulation of RORC, IL17A, and TNFA. However, the mechanisms that cause these higher mRNA expression levels in this asthmatic phenotype are poorly understood. Methylation directly regulates gene expression by adding a methyl group to carbon 5 of dinucleotide CpG cytosine. Thus, we evaluated the relationship between RORC, IL17A, and TNFA methylation status and mRNA expression levels to investigate a possible epigenetic regulation. A total of 102 adolescents (11–18 years) were studied in the following four groups: 1) healthy participants (HP), 2) allergic asthmatic participants (AAP), 3) obese participants without asthma (OP), and 4) non-allergic obesity-related asthma participants (OAP). Real-time qPCR assessed the methylation status and gene expression levels in peripheral blood leukocytes. Remarkably, the OAP and AAP groups have lower promoter methylation patterns of RORC, IL17A, and TNFA than the HP group. Notably, the OAP group presents lower RORC promoter methylation status than the OP group. Interestingly, RORC promoter methylation status was moderately negatively associated with gene expression of RORC (rs = −0.39, p < 0.001) and IL17A (rs = −0.37, p < 0.01), respectively. Similarly, the promoter methylation pattern of IL17A was moderately negatively correlated with IL17A gene expression (rs = −0.3, p < 0.01). There is also a moderate inverse relationship between TNFA promoter methylation status and TNFA gene expression (rs = −0.3, p < 0.01). The present study suggests an association between lower RORC, IL17A, and TNFA gene promoter methylation status with obesity-related asthma and allergic asthma. RORC, IL17A, and TNFA gene promoter methylation patterns are moderately inversely correlated with their respective mRNA expression levels. Therefore, DNA methylation may regulate RORC, IL17A, and TNF gene expression in both asthmatic phenotypes.
