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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #338363

Research Project: Genomics, Nutrition, and Health

Location: Jean Mayer Human Nutrition Research Center On Aging

Title: TNFA gene variants related to the inflammatory status and its association with cellular aging: From the CORDIOPREV study

Author
item RANGEL ZÚÑIGA, ORIOL ALBERTO - Universidad De Cordoba
item CORINA, ANDREEA - Universidad De Cordoba
item LUCENA-PORRAS, BEATRIZ - Universidad De Cordoba
item CRUZ-TENO, CRISTINA - Universidad De Cordoba
item GÓMEZ-DELGADO, FRANCISCO - Universidad De Cordoba
item JIMÉNEZ-LUCENA, ROSA - Universidad De Cordoba
item ALCALÁ DÍAZ, JUAN FRANCISCO - Universidad De Cordoba
item HARO MARISCAL, CARMEN - Universidad De Cordoba
item YUBERO-SERRANO, ELENA MARIA - Universidad De Cordoba
item DELGADO-LISTA, JAVIER - Universidad De Cordoba
item LÓPEZ MORENO, JAVIER - Universidad De Cordoba
item RODRIGUEZ-CANTEALEJO, FERNANDO - University Hospital Reina Sofia
item CARMARGO, ANTONIO - Universidad De Cordoba
item TINAHONES, FRNCISCO JOSE - Hospital Universitario Virgen De La Victoria
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item LÓPEZ MIRANDA, JOSE - Universidad De Cordoba
item PÉREZ MARTÍNEZ, PABLO - Universidad De Cordoba

Submitted to: Experimental Gerontology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/27/2016
Publication Date: 7/29/2016
Citation: Rangel Zúñiga, O., Corina, A., Lucena-Porras, B., Cruz-Teno, C., Gómez-Delgado, F., Jiménez-Lucena, R., Alcalá Díaz, J., Haro Mariscal, C., Yubero-Serrano, E., Delgado-Lista, J., López Moreno, J., Rodriguez-Cantealejo, F., Carmargo, A., Tinahones, F., Ordovas, J.M., López Miranda, J., Pérez Martínez, P. 2016. TNFA gene variants related to the inflammatory status and its association with cellular aging: From the CORDIOPREV study. Experimental Gerontology. 83:56–62.

Interpretive Summary: Elevated chronic inflammation is one of the hallmarks of aging and age-related diseases. In addition, telomere length has been proposed as a measure of biological aging. However, it is not well known how inflammation affects the rate of telomere shortening and whether this relation may also have a genetic component. The objective of this research was to investigate whether gene variants within the Tumor Necrosis Factor Alpha (TNFA) were associated with inflammatory status and the rate of telomere shortening and whether this could be related to cellular aging in a population with established cardiovascular disease (the CORDIOPREV study.) For this purpose we genotyped and determined relative telomere length of two single nucleotide polymorphisms SNPs) (rs1800629 and rs1799964.) Our data indicate that GG subjects for the TNFA SNP, known as rs1800629, had shorter relative telomere length and higher levels of inflammation than A-allele subjects. 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. In summary, subjects carrying the GG genotype for the SNP rs1800629 at the TNFA gene show a greater proinflammatory status than A-allele carriers, which is related to increased oxidation and to DNA damage especially in the telomeric sequence. The results of these combined effects suggest that GG subjects will have accelerated aging and age-related diseases.

Technical Abstract: Background: Several single nucleotide polymorphisms have been proposed as potential predictors of the development of age-related diseases. Objective: 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). Materials and methods: 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, IKKbeta, p47phox, p40phox, p22phox and gp91phox were determined by qRT-PCR. Results: 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 proinflammatory (TNFA) and pro-oxidant (p47phox and the gp91phox) genes was higher in GG subjects than A allele subjects (p<0.05). Conclusion: 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.