Razquin, C. (Cristina)
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- Adherence to Mediterranean diet is associated with methylation changes in inflammation-related genes in peripheral blood cells(Springer, 2017-02-08) Martinez, J.A. (José Alfredo); Riezu-Boj, J.I. (José Ignacio); Martinez-Gonzalez, M.A. (Miguel Ángel); Fito, M. (Montserrat); Milagro-Yoldi, F.I. (Fermín Ignacio); Arpon, A. (Ana); Razquin, C. (Cristina); Ros, E. (Emilio); Casas, R. (Rosa); Estruch, R. (Ramón); Corella, D. (Dolores); Salas-Salvado, J. (Jordi)Epigenetic processes, including DNA methylation, might be modulated by environmental factors such as the diet, which in turn have been associated with the onset of several diseases such as obesity or cardiovascular events. Meanwhile, Mediterranean diet (MedDiet) has demonstrated favourable effects on cardiovascular risk, blood pressure, inflammation and other complications related to excessive adiposity. Some of these effects could be mediated by epigenetic modifications. Therefore, the objective of this study was to investigate whether the adherence to MedDiet is associated with changes in the methylation status from peripheral blood cells. A subset of 36 individuals was selected within the Prevención con Dieta Mediterránea (PREDIMED)-Navarra study, a randomised, controlled, parallel trial with three groups of intervention in high cardiovascular risk volunteers, two with a MedDiet and one low-fat control group. Changes in methylation between baseline and 5 years were studied. DNA methylation arrays were analysed by several robust statistical tests and functional classifications. Eight genes related to inflammation and immunocompetence (EEF2, COL18A1, IL4I1, LEPR, PLAGL1, IFRD1, MAPKAPK2, PPARGC1B) were finally selected as changes in their methylation levels correlated with adherence to MedDiet and because they presented sensitivity related to a high variability in methylation changes. Additionally, EEF2 methylation levels positively correlated with concentrations of TNF-α and CRP. This report is apparently the first showing that adherence to MedDiet is associated with the methylation of the reported genes related to inflammation with a potential regulatory impact.
- Arginine catabolism metabolites and atrial fibrillation or heart failure risk: 2 case-control studies within the Prevención con Dieta Mediterránea (PREDIMED) trial(Oxford University Press, 2022) Babio, N. (Nancy); Martinez-Gonzalez, M.A. (Miguel Ángel); Fiol, M. (Miquel); Clish, C.B. (Clary B.); Atzeni, A. (Alessandro); Fito, M. (Montserrat); Hu, F.B. (Frank B.); Wittenbecher, C. (Clemens); Li, J. (Jun); Gomez-Gracia, E. (Enrique); Toledo, E. (Estefanía); Goñi-Mateos, L. (Leticia); Lapetra, J. (José); Guasch-Ferre, M. (Marta); Razquin, C. (Cristina); Liang, L. (Liming); Ros, E. (Emilio); Ruiz-Canela, M. (Miguel); Alonso-Gomez, A. (Ángel); Dennis, C. (Courtney); Estruch, R. (Ramón); Serra-Majem, L. (Luis); Corella, D. (Dolores); Salas-Salvado, J. (Jordi); Aros, F. (Fernando)Background Arginine-derived metabolites are involved in oxidative and inflammatory processes related to endothelial functions and cardiovascular risks. Objectives We prospectively examined the associations of arginine catabolism metabolites with the risks of atrial fibrillation (AF) or heart failure (HF), and evaluated the potential modifications of these associations through Mediterranean diet (MedDiet) interventions in a large, primary-prevention trial. Methods Two nested, matched, case-control studies were designed within the Prevención con Dieta Mediterránea (PREDIMED) trial. We selected 509 incident cases and 547 matched controls for the AF case-control study and 326 cases and 402 matched controls for the HF case-control study using incidence density sampling. Fasting blood samples were collected at baseline and arginine catabolism metabolites were measured using LC-tandem MS. Multivariable conditional logistic regression models were applied to test the associations between the metabolites and incident AF or HF. Interactions between metabolites and intervention groups (MedDiet groups compared with control group) were analyzed with the likelihood ratio test. Results Inverse association with incident AF was observed for arginine (OR per 1 SD, 0.83; 95% CI: 0.73–0.94), whereas a positive association was found for N1-acetylspermidine (OR for Q4 compared with Q1 1.58; 95% CI: 1.13–2.25). For HF, inverse associations were found for arginine (OR per 1 SD, 0.82; 95% CI: 0.69–0.97) and homoarginine (OR per 1 SD, 0.81; 95% CI: 0.68–0.96), and positive associations were found for the asymmetric dimethylarginine (ADMA) and symmetric dimethlyarginine (SDMA) ratio (OR per 1 SD, 1.19; 95% CI: 1.02–1.41), N1-acetylspermidine (OR per 1 SD, 1.34; 95% CI: 1.12–1.60), and diacetylspermine (OR per 1 SD, 1.20; 95% CI: 1.02–1.41). In the stratified analysis according to the dietary intervention, the lower HF risk associated with arginine was restricted to participants in the MedDiet groups (P-interaction = 0.044). Conclusions Our results suggest that arginine catabolism metabolites could be involved in AF and HF. Interventions with the MedDiet may contribute to strengthen the inverse association between arginine and the risk of HF. This trial was registered at controlled-trials.com as ISRCTN35739639.
- Mediterranean diet and telomere length in high cardiovascular risk subjects from the PREDIMED-NAVARRA study(Elsevier, 2016-12) Martinez, J.A. (José Alfredo); Martinez-Gonzalez, M.A. (Miguel Ángel); Lapetra, J. (José); Razquin, C. (Cristina); Garcia-Calzon, S. (Sonia); Zalba, G. (Guillermo); Aros, F. (Fernando); Marti-del-Moral, A. (Amelia)Summary Background & aims A healthy lifestyle has been associated with longer telomeres, but whether Mediterranean Diet (MeDiet) affect telomere length (TL) has not been fully elucidated yet. Our aim was to assess the relationship between MeDiet and TL in high cardiovascular risk subjects in the context of a randomized nutritional intervention trial. Methods We assessed 520 participants (55–80 years, 55% women) from the PREDIMED-NAVARRA trial. Leukocyte TL was measured by qPCR at baseline and after 5 years of a dietary intervention program where subjects were randomly assigned to a low-fat control diet or to two MeDiets, one supplemented with extra virgin olive oil (MeDiet-EVOO) and the other with mixed nuts (MeDiet-nuts). A validated 14-item questionnaire was used to appraise baseline adherence of participants to the MeDiet. Results Better adherence to MeDiet (as appraised by the 14-item score) was associated with longer basal telomeres in women in the baseline cross-sectional analysis, whereas the opposite was observed in men (P interaction = 0.036). Female subjects who scored 10 points had longer basal telomeres (0.27, 95% CI: 0.03–0.52) than women scoring ≤6 points at the beginning of the study (−0.46, 95% CI: −0.85 to −0.7) (P = 0.003). However, allocation to the MeDiet-nuts group (−0.24, 95% CI: −0.38 to −0.01) was associated with a higher risk of telomere shortening after 5 years of intervention, whereas no differences were found for the MeDiet-EVOO group (0.14, 95% CI: 0.02–0.27), in comparison with the Control group (0.07, 95% CI: −0.08 to 0.23) (P = 0.003 and P = 0.537, respectively). Conclusion A greater baseline adherence to a Mediterranean dietary pattern was associated with longer telomeres only in women. No beneficial effect of the intervention with the MeDiet for the prevention of telomere shortening in comparison with a low-fat diet was observed.
- Elevated levels of the complement activation product c4d in bronchial fluids for the diagnosis of lung cancer(Public Library of Science, 2015) Pajares, M.J. (María José); Garcia, J. (Javier); Pio, R. (Rubén); Lozano, M.D. (María Dolores); Schmidt, B. (Bernd); Fleischhacker, M. (M.); Nadal, E. (Ernest); Montuenga-Badia, L.M. (Luis M.); Razquin, C. (Cristina); Paz-Ares, L. (Luis); Ajona, D. (Daniel); Pastor, M.D. (María Dolores); Cardenal, F. (F.); Zulueta, J. (Javier)Molecular markers in bronchial fluids may contribute to the diagnosis of lung cancer. We previously observed a significant increase of C4d-containing complement degradation fragments in bronchoalveolar lavage (BAL) supernatants from lung cancer patients in a cohort of 50 cases and 22 controls (CUN cohort). The present study was designed to determine the diagnostic performance of these complement fragments (hereinafter jointly referred as C4d) in bronchial fluids. C4d levels were determined in BAL supernatants from two independent cohorts: the CU cohort (25 cases and 26 controls) and the HUVR cohort (60 cases and 98 controls). A series of spontaneous sputum samples from 68 patients with lung cancer and 10 controls was also used (LCCCIO cohort). Total protein content, complement C4, complement C5a, and CYFRA 21-1 were also measured in all cohorts. C4d levels were significantly increased in BAL samples from lung cancer patients. The area under the ROC curve was 0.82 (95%CI = 0.71-0.94) and 0.67 (95%CI = 0.58-0.76) for the CU and HUVR cohorts, respectively. In addition, unlike the other markers, C4d levels in BAL samples were highly consistent across the CUN, CU and HUVR cohorts. Interestingly, C4d test markedly increased the sensitivity of bronchoscopy in the two cohorts in which cytological data were available (CUN and HUVR cohorts). Finally, in the LCCCIO cohort, C4d levels were higher in sputum supernatants from patients with lung cancer (area under the ROC curve: 0.7; 95%CI = 0.56-0.83). In conclusion, C4d is consistently elevated in bronchial fluids from lung cancer patients and may be used to improve the diagnosis of the disease.
- Biochemical profile, eating habits, and telomere length among Brazilian children and adolescents(Elsevier, 2020) Martinez, J.A. (José Alfredo); Milagro-Yoldi, F.I. (Fermín Ignacio); Rech-Franke, S.I. (Silvia Isabel); Fiegenbaum, M. (Marilu); Ferreira-Todendi, P. (Pamela); Razquin, C. (Cristina); Silva-Kahl, V.F. (Vivian Francilia); Latosinski-Matos, W. (William); Moura-Valim, A.R. (Andreia Rosane) de; Priscila-Reuter, C. (Cezane)Objectives: Lifestyle, obesity, and eating habits are emerging as determinants for the instability of telomeres. The increase in childhood and adolescent obesity and the association of biochemical profiles and dietary components with telomere length (TL) makes it an important issue in nutritional research. The aim of the present study was to investigate TL and its association with ethnic background, adiposity, clinical and biochemical parameters, and dietary patterns among Brazilian children and adolescents. Methods: A cross-sectional study encompassing 981 children and adolescents between 7 and 17 y of age was performed. Dietary intake habits, anthropometry, and clinical data were collected. TL analysis was performed by quantitative polymerase chain reaction. Results: Children presented significantly longer TL than adolescents (P = 0.046). Participants who self-declared as black, mulatto, or brown (P < 0.001) also showed longer TL than those who were white. Regarding biochemical parameters, individuals with altered glucose levels had shorter TL than normoglycemic participants in the total sample (P = 0.014). Such difference remained statistically significant in adolescents (P = 0.019). Participants who reported eating fruits and vegetables regularly had longer TL than those who did not (P < 0.001). Conclusion: The results suggested that both biochemical parameters and the intake of antioxidant-rich food, such as fruits and vegetables, are associated with the stability of telomere biology among young Brazilians.
- Fatty Acids Composition of Blood Cell Membranes and Peripheral Inflammation in the PREDIMED Study: A Cross-Sectional Analysis(MDPI AG, 2019) Castañer, O. (Olga); Martinez-Gonzalez, M.A. (Miguel Ángel); Fito, M. (Montserrat); Rosique-Esteban, N. (Nuria); Sala-Vila, A. (Aleix); Muralidharan, J. (Jananee); Papandreou, C. (Christopher); Razquin, C. (Cristina); Ros, E. (Emilio); Bullo, M. (Monica); Estruch, R. (Ramón); Corella, D. (Dolores); Salas-Salvado, J. (Jordi)There is limited evidence from epidemiological studies for the inflammatory or anti-inflammatory properties of fatty acids in blood cell membranes. Therefore, this study examined associations between baseline (n = 282) and 1-year (n = 143) changes in the levels of fatty acids in blood cell membranes with circulating inflammatory markers in older adults at high cardiovascular risk. The data for this cross-sectional analysis was obtained from a case-control study within the PREDIMED study. Linear regression with elastic net penalty was applied to test associations between measured fatty acids and inflammatory markers. Several fatty acids were associated with interferon-γ (IFNγ) and interleukins (ILs) IL-6, IL-8, and IL-10 at baseline and additionally also with IL-1b at 1 year. Omega-6 fatty acids were consistently positively associated with pro-inflammatory IL-6 and IL-8 at baseline. Omega-3 fatty acids including C20:5n3 and C18:3n3 were negatively associated with IFN-γ at 1 year. It is interesting to note that the cis and trans forms of C16:1n7 at 1 year were oppositely associated with the inflammatory markers. C16:1n7trans was negatively associated with IFN-γ, IL-6, IL-8, IL-10, and IL-1b, whereas C16:1n7cis was positively associated with IL-1b. This study adds to the growing body of evidence suggesting potential differences in inflammatory or anti-inflammatory properties of fatty acids in blood cell membranes.
- Increase from low to moderate, but not high, caffeinated coffee consumption is associated with favorable changes in body fat(2023) Babio, N. (Nancy); Buil, P. (Pilar); Fito, M. (Montserrat); Hu, F.B. (Frank B.); Konieczna, J. (Jadwiga); Vioque, J. (Jesús); Zulet, M.A. (María Ángeles); Romaguera, D. (Dora); Fernández-Villa, T. (Tania); Schröder, H. (Helmut); Razquin, C. (Cristina); Estruch, R. (Ramón); Vazquez-Ruiz, Z. (Zenaida); Henn, M. (Matthias); Abete, I. (Itziar); Vidal, J. (Josep); Martin, V. (Vicente); Torres-Collado, L. (Laura)
- Changes in plasma total saturated fatty acids and palmitic acid are related to pro-inflammatory molecule IL-6 concentrations after nutritional intervention for one year(2022) Martinez-Gonzalez, M.A. (Miguel Ángel); Fito, M. (Montserrat); Hu, F.B. (Frank B.); Lopez-Sabater, M.C. (M. Carmen); Domínguez-López, I. (Inés); Tresserra-Rimbau, A. (Anna); Razquin, C. (Cristina); Ros, E. (Emilio); Casas, R. (Rosa); Estruch, R. (Ramón); Lamuela-Raventos, R.M. (Rosa Maria); Arancibia-Riveros, C. (Camila)Systemic inflammation is associated with an increased risk of non-communicable diseases, such as cardiovascular diseases and diabetes. Circulating fatty acids (FA) are known to be related to these conditions, possibly through their role in inflammation, although different types of FAs can have opposite effects on inflammatory mediators. The aim of the present study was to analyze the association of plasma FAs with inflammatory biomarkers in a PREDIMED trial subsample after one year of intervention. In a one-year longitudinal study of 91 participants of the PREDIMED trial (Barcelona-Clinic center), plasma FAs and inflammatory biomarkers were analyzed using gas chromatography and ELISA, respectively. In baseline plasma, a multivariable-adjusted ordinary least squares regression model showed that n-3 polyunsaturated FAs concentrations were inversely associated with concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and E-selectin, whereas the level of the most abundant saturated FA, palmitic acid, was directly associated with concentrations of interleukin-6 (IL-6) (beta = 0.48 pg/mL, 95% CI: 0.03, 0.93 per 1-SD increase, p-value = 0.037). After one year of nutritional intervention, changes of plasma diet-derived total saturated FAs and palmitic acid were directly associated with changes in IL6 (beta = 0.59 pg/mL [95% CI: 0.28, 0.89] per 1-SD, p-value = 0.001; beta = 0.64 pg/mL, 95% CI: 0.31, 0.98, p-value = 0.001), respectively, after correction for multiple testing. Our findings suggest that saturated FAs of dietary origin, especially palmitic acid, are directly involved in the increase of IL-6 in plasma.
- Egg consumption and dyslipidemia in a Mediterranean cohort(Aran, 2018) Martinez-Gonzalez, M.A. (Miguel Ángel); Fuente-Arrillaga, C. (Carmen) de la; Zazpe, I. (Itziar); Toledo, E. (Estefanía); Bes-Rastrollo, M. (Maira); Santiago, S. (Susana); Razquin, C. (Cristina); Vazquez-Ruiz, Z. (Zenaida)Introduction and objectives: Our aim was to prospectively evaluate the association between egg consumption and dyslipidemia in a Mediterranean cohort. Methods: We followed-up 13,104 Spanish university graduates for a mean period of 8 years. Dietary habits at baseline were assessed using a validated semi-quantitative 136-item food-frequency questionnaire. Self-reported blood concentrations of total cholesterol, high-density lipoproteins cholesterol (HDL-c) and triglycerides were evaluated according to categories of egg consumption after 6 and 8 years of follow-up. We also assessed the association between baseline egg consumption and the incidence of hypercholesterolemia, low HDL-c concentrations and hypertriglyceridemia during follow-up. Results: We observed a significant inverse association for intermediate levels of egg consumption (2 to 4 eggs/week vs. less than 1 egg/week) and hypertriglyceridemia with OR = 0.71 (95% confidence interval [CI]: 0.54 to 0.93, p < 0.05) in the multivariable-adjusted model. Using HDL-c values after 8-year follow-up, we found an association between higher egg consumption and lower HDL-c levels (p for trend = 0.02) with an adjusted difference of –4.01 mg/dl (-7.42 to -0.61) for > 4 vs. < 1 egg/week. Lower means of triglycerides were found in each of the three upper categories of egg consumption compared to the lowest category (< 1 egg/week) with significant results for some of these categories both after 6 and 8 year follow-up. Conclusions: Our data do not support that higher egg consumption was associated with abnormal blood levels of total cholesterol or triglycerides; an inverse association with HDL-c as a quantitative variable was found only in one of our analyses.
- A novel mutation Thr162Arg of the melanocortin 4 receptor gene in a Spanish children and adolescent population(Wiley Blackwell, 2007) Martinez, J.A. (José Alfredo); Wermter, A.K. (A.K.); Hinney, A. (Anke); Moreno-Aliaga, M. J. (María Jesús); Hebebrand, J. (Joahnnes); Ochoa, M.C. (María Carmen); Razquin, C. (Cristina); Azcona-San-Julian, M.C. (María Cristina); Brumm, H. (H.); Biebermann, H. (H.); Grupo de Estudio Navarro de la Obesidad Infantil (GENOI); Marti-del-Moral, A. (Amelia)Objective The melanocortin 4 receptor gene (MC4R) is involved in body weight regulation. While many studies associated MC4R mutations with childhood obesity, information on MC4R mutations in Spanish children and adolescents is lacking. Our objective was to screen a population of children and adolescents from the north of Spain (Navarra) for MC4R mutations and to study the phenotypes of carriers and their families. In addition, functional assays were performed for a novel MC4R mutation. Methods The study was composed of 451 Spanish children and adolescents (49% boys), aged 5–18 year. According to the International Obesity Task Force (IOTF) criteria, the groups included 160 obese, 132 overweight and 159 normal-weight control subjects. Results One novel (Thr162Arg) and three known nonsynonymous mutations in the MC4R gene (Ser30Phe, Thr150Ile, Ala244Glu) were detected heterozygously. The MC4R mutations were found in three male (one obese and two overweight) and two female subjects (one obese and one overweight). The novel mutation did not appear to lead to an impaired receptor function. An unequivocal relationship of MC4R mutations with obesity in pedigrees together with an impaired function of the encoded receptor could not be established for any of the mutations. Conclusions The presence of heterozygous MC4R mutations in obese and overweight subjects indicates that these mutations may be a susceptibility factor for obesity development, but lifestyle factors, such as exercise or sedentary activities, may modify their effect.