Telomerase RNA Component (TERC) genetic variants interact with the mediterranean diet modifying the inflammatory status and its relationship with aging: CORDIOPREV study

Authors: GOMEZ-DELGADO, FRANCISCO - UNIVERSIDAD DE CORDOBA; DELGADO-LISTA, JAVIER - UNIVERSIDAD DE CORDOBA; LOPEZ-MORENO, JAVIER - UNIVERSIDAD DE CORDOBA; RANGEL-ZUÑIGA, ORIOL - UNIVERSIDAD DE CORDOBA; ALCALA-DIAZ, JUAN FANCISCO - UNIVERSIDAD DE CORDOBA; LEON ACUÑA, ANA - UNIVERSIDAD DE CORDOBA; BABA, ANDREEA - UNIVERSIDAD DE CORDOBA; YUBERO-SERRANO, ELENA - UNIVERSIDAD DE CORDOBA; TORRES PEÑA, JOSE DAVID - UNIVERSIDAD DE CORDOBA; CAMARGO, ANTONIO - UNIVERSIDAD DE CORDOBA; GARCIA-RIOS, ANTONIO - UNIVERSIDAD DE CORDOBA; CABELLERO, JAVIER - REINA SOFIA UNIVERSITY; CASTAÑO, JAVIER - UNIVERSIDAD DE CORDOBA; ORDOVAS, JOSE - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; LOPEZ-MIRANDA, JOSE - UNIVERSIDAD DE CORDOBA; PEREZ-MARTINEZ, PABLO - UNIVERSIDAD DE CORDOBA

Submitted to: Journal of Gerontology Medical Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/13/2016
Publication Date: 10/5/2016
Citation: Gomez-Delgado, F., Delgado-Lista, J., Lopez-Moreno, J., Rangel-Zuñiga, O., Alcala-Diaz, J., Leon Acuña, A., Baba, A.C., Yubero-Serrano, E., Torres Peña, J., Camargo, A., Garcia-Rios, A., Cabellero, J., Castaño, J., Ordovas, J.M., Lopez-Miranda, J., Perez-Martinez, P. 2016. Telomerase RNA Component (TERC) genetic variants interact with the mediterranean diet modifying the inflammatory status and its relationship with aging: CORDIOPREV study. Journal of Gerontology Medical Science. doi: 10.1093/gerona/glw194.

Interpretive Summary: Telomeres are regions of repetitive nucleotide sequences at each end of a chromosome that protect the chromosome's ends from deterioration or from fusion with other chromosomes. Telomere length shortens with age. Progressive shortening of telomeres leads to senescence, which affects the health and lifespan of an individual. Shorter telomeres have been associated with increased incidence of diseases and poor survival rates. The rate of telomere shortening can be either increased or decreased by specific lifestyle factors. Better choice of diet and activities has great potential to reduce the rate of telomere shortening or at least prevent excessive telomere attrition. The objective of this work was to explore whether genetic variability at the TERC gene locus known as TERC (Telomerase RNA Component) interacts with plasma fatty acids profile and two healthy diets (low-fat (LF) diet vs. Mediterranean diet (MedDiet) modulating leukocyte telomere length, glucose metabolism and inflammation status in 1,002 individuals with coronary heart disease. Our results show that a genetic variant in TERC known as rs12696304 interacted with plasma total monounsaturated fatty acids (MUFA) modulating the levels of the inflammatory biomarker C-reactive protein (hsCRP) and the leukocyte telomere length. Among subjects with high MUFA levels, carriers of the CC genotype showed lower hsCRP and higher LTL than G-allele carriers. After 12 months of dietary intervention, we found also a significant gene-diet interaction between TERC rs12696304 SNP and the MedDiet. Specifically, CC subjects displayed a greater decrease in hsCRP than G-allele carriers (GG + CG). Our findings indicate that genetic variation at the TERC gene interacts with MUFA, improving inflammation status and telomere attrition related with coronary heart disease.

Technical Abstract: Background: Leukocyte telomere length (LTL) attrition has been associated with age-related diseases. Telomerase RNA Component (TERC) genetic variants have been associated with LTL; whereas fatty acids (FAs) can interact with genetic factors and influence in aging. We explore whether variability at the TERC gene locus interacts with FA profile and two healthy diets (low-fat diet vs Mediterranean diet [MedDiet]) modulating LTL, glucose metabolism, and inflammation status in coronary heart disease (CHD) patients. Methods: Inflammation status (high-sensitivity C-reactive protein [hsCRP], glucose metabolism-glucose, insulin, and glycated hemoglobin [HbA1c], and homeostasis model assessment of insulin resistance [HOMA-IR]), LTL, FAs, and single nucleotide polymorphisms (SNPs) of the TERC gene (rs12696304, rs16847897, and rs3772190) were determined in 1,002 patients from the CORDIOPREV study (NCT00924937). Results: We report an interaction of the TERC rs12696304 SNP with monounsaturated fatty acid (MUFA) affecting LTL (p interaction = .01) and hsCRP (p interaction = .03). Among individuals with MUFA levels above the median, CC individuals showed higher LTL and lower hsCRP than G-allele carriers. Moreover, MedDiet interacted with TERC rs12696304 SNP (p interaction = .03). Specifically, CC individuals displayed a greater decrease in hsCRP than G-allele carriers. These results were not adjusted for multiple statistical testing and p less than .05 was considered significant. Conclusions: Our findings suggest that the TERC rs12696304 SNP interacts with MUFA improving inflammation status and telomere attrition related with CHD. Moreover, the MedDiet intervention improves the inflammatory profile in CC individuals compared with the G-allele carriers. These interactions could provide a right strategy for personalized nutrition in CHD patients.