title: TNFA gene variants related to the inflammatory status and its association with cellular aging: From the CORDIOPREV study.
abstract: Several single nucleotide polymorphisms have been proposed as potential predictors of the development of age-related diseases.
  
  
  
  To explore whether Tumor Necrosis Factor Alpha (TNFA) gene variants were associated with inflammatory status, thus facilitating the rate of telomere shortening and its relation to cellular aging in a population with established cardiovascular disease from the CORDIOPREV study (NCT00924937).
  
  
  
  SNPs (rs1800629 and rs1799964) located at the TNFA gene were genotyped by OpenArray platform in 840 subjects with established cardiovascular disease. Relative telomere length was determined by real time PCR and plasma levels of C-reactive protein by ELISA. In a subgroup of 90 subjects, the gene expression profiles of TNFA, IKKβ, p47phox, p40phox, p22phox and gp91phox were determined by qRT-PCR.
  
  
  
  GG subjects for the SNP rs1800629 at the TNFA gene showed shorter relative telomere length and higher plasma levels of hs-CRP than A-allele subjects (p<0.05). Consistent with these findings, the expression of pro-inflammatory (TNFA) and pro-oxidant (p47phox and the gp91phox) genes was higher in GG subjects than A allele subjects (p<0.05).
  
  
  
  Subjects carrying the GG genotype for the SNP rs1800629 at the TNFA gene show a greater activation of the proinflammatory status than A-allele carriers, which is related to ROS formation. These ROS could induce DNA damage especially in the telomeric sequence, by decreasing the telomere length and inducing cellular aging. This effect may also increase the risk of the development of age-related diseases.
authors.affiliation: Lipids and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Córdoba, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Oriol Alberto
authors.initials: OA
authors.lastname: Rangel-Zúñiga
authors.affiliation: Lipids and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Córdoba, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Andreea
authors.initials: A
authors.lastname: Corina
authors.affiliation: Lipids and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Córdoba, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Lucena-Porras
authors.affiliation: Lipids and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Córdoba, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cruz-Teno
authors.affiliation: Lipids and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Córdoba, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Gómez-Delgado
authors.affiliation: Lipids and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Córdoba, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Jiménez-Lucena
authors.affiliation: Lipids and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Córdoba, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Juan Francisco
authors.initials: JF
authors.lastname: Alcalá-Díaz
authors.affiliation: Lipids and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Córdoba, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Haro-Mariscal
authors.affiliation: Lipids and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Córdoba, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Elena María
authors.initials: EM
authors.lastname: Yubero-Serrano
authors.affiliation: Lipids and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Córdoba, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Delgado-Lista
authors.affiliation: Lipids and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Córdoba, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: López-Moreno
authors.affiliation: Biochemical Laboratory, Reina Sofia University Hospital, Córdoba, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodríguez-Cantalejo
authors.affiliation: Lipids and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Córdoba, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Camargo
authors.affiliation: CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain; Biomedical Research Laboratory, Endocrinology Department, Hospital Virgen de la Victoria, Malaga, Spain.
authors.forename: Francisco José
authors.initials: FJ
authors.lastname: Tinahones
authors.affiliation: Nutrition and Genomics Laboratory, J.M,-US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA; IMDEA-Food and CNIC, Madrid, Spain.
authors.forename: José María
authors.initials: JM
authors.lastname: Ordovás
authors.affiliation: Lipids and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Córdoba, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: José
authors.initials: J
authors.lastname: López-Miranda
authors.affiliation: Lipids and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Córdoba, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: pablopermar@yahoo.es.
authors.forename: Pablo
authors.initials: P
authors.lastname: Pérez-Martínez
mesh_terms: D000368:Aged; D000483:Alleles; D002097:C-Reactive Protein / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008297:Male; D018384:Oxidative Stress; D020641:Polymorphism, Single Nucleotide; D016032:Randomized Controlled Trials as Topic; D017382:Reactive Oxygen Species / Q000378:metabolism; D013030:Spain; D016615:Telomere / Q000648:ultrastructure; D059506:Telomere Shortening; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D017382:Reactive Oxygen Species; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein
keywords: CORDIOPREV study; Cellular aging; Inflammation; Oxidative stress; TNFA genetic variants; Telomere length