Open Access
Association between UCP1, UCP2, and UCP3 gene polymorphisms with markers of adiposity in European adolescents: The HELENA study
(Wiley, 2019) Pascual Gamarra, José Miguel; Salazar-Tortosa, Diego; Martínez Téllez, Borja; Labayen Goñi, Idoia; Rupérez, Azahara I.; Censi, Laura; Manios, Yannis; Nova, Esther; Gesteiro, Eva; Moreno, Luis A.; Meirhaeghe, Aline; Ruiz, Jonatan R.; Osasun Zientziak; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD; Ciencias de la Salud
Aims: To examine the association between UCP1, UCP2, and UCP3 gene polymorphisms with adiposity markers in European adolescents and to test if there were gene interactions with objectively measured physical activity and adiposity. Methods: A cross-sectional study that involves 1.057 European adolescents (12-18 years old) from the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study. A total of 18 polymorphisms in UCP1, UCP2, and UCP3 genes were genotyped. We measured weight, height, waist, and hip circumferences and triceps and subscapular skinfold thickness. Physical activity was objectively measured by accelerometry during 7 days. Results: The C allele of the UCP1 rs6536991 polymorphism was associated with a lower risk of overweight (odds ratio [OR]: T/C + C/C vs T/T) = 0.72; 95% confidence interval [CI]: 0.53-0.98; P = 0.034; false discovery rate [FDR] = 0.048). There was a significant interaction between UCP1 rs2071415 polymorphism and physical activity with waist-to-hip ratio (P = 0.006; FDR = 0.026). Adolescents who did not meet the physical activity recommendations (less than 60 min/day of moderate to vigorous physical activity) and carrying the C/C genotype had higher waist-to-hip ratio (+ 0.067; 95% CI, 0.028-0.106; P = 0.003), while no differences across genotypes were observed in adolescents meeting the recommendations. Conclusions: Two UCP1 polymorphisms were associated with adiposity in European adolescents. Meeting the daily physical activity recommendations may overcome the effect of the UCP1 rs2071415 polymorphism on obesity-related traits.
Open Access
Interplay of the mediterranean diet and genetic hypertension risk on blood pressure in european adolescents: findings from the HELENA study
(Springer, 2024) Pérez-Gimeno, Gloria; Seral-Cortes, Miguel; Sabroso-Lasa, Sergio; Esteban, Luis Mariano; Widhalm, Kurt; Gottrand, Frédéric; Stehle, Peter; Meirhaeghe, Aline; Muntaner, Manon; Kafatos, Antonios; Gutiérrez, Ángel; Manios, Yannis; Anastasiou, Costas A.; González Gross, Marcela; Breidenassel, Christina; Censi, Laura; Henauw, Stefaan de; Labayen Goñi, Idoia; Bueno-Lozano, Gloria; Rupérez, Azahara I.; Moreno, Luis A.; Ciencias de la Salud; Osasun Zientziak; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD
Early-life onset of high blood pressure is associated with the development of cardiovascular diseases in adulthood. In adolescents, limited evidence exists regarding the association between adherence to the Mediterranean Diet (MedDiet) and normal blood pressure (BP) levels, as well as its potential to modulate genetic predisposition to HTN. This study investigated the interaction between a MedDiet score and a recently developed HTN-genetic risk score (HTN-GRS) on blood pressure levels in a European adolescent cohort. The MedDiet score was derived from two non-consecutive 24-h dietary recalls and ranged from 0 (indicating low adherence) to 9 (indicating high adherence). Multiple linear regression models, adjusted for covariates, were employed to examine the relationship between the MedDiet score and BP z-scores and to assess the interaction effects between the MedDiet score and HTN-GRS on BP z-scores. MedDiet score showed a negative association with z-systolic BP (SBP) (ß = -0.40, p < 0.001) and z-diastolic BP (DBP) (ß = -0.29, p = 0.001). Additionally, a significant interaction effect was identified between the MedDiet score and HTN-GRS on z-SBP (ß = 0.02, p < 0.001) and z-DBP (ß = 0.02, p < 0.001). The modulatory effect of the MedDiet was more pronounced in females than in males, and HTN-GRS exhibited a stronger influence on DBP than on SBP. Conclusion: The study suggests that higher adherence to the MedDiet is associated with reduced BP levels in adolescents and provides evidence of a genetic-diet interaction influencing BP in adolescents. (Table presented.)
Open Access
The body mass index increases the genetic risk scores' ability to predict risk of hepatic damage in European adolescents: the HELENA study
(Wiley, 2023) Seral-Cortes, Miguel; Sabroso-Lasa, Sergio; González Gross, Marcela; Quesada-González, Carlos; Stehle, Peter; Gottrand, Frédéric; Marcos, Ascensión; Diaz, Ligia Esperanza; Manios, Yannis; Androutsos, Odysseas; Widhalm, Kurt; Molnár, Dénes; Huybrechts, Inge; Muntaner, Manon; Meirhaeghe, Aline; Salazar-Tortosa, Diego; Ruiz, Jonatan R.; Esteban, Luis Mariano; Labayen Goñi, Idoia; Moreno, Luis A.; Ciencias de la Salud; Osasun Zientziak
Background: Hepatic disorders are often complex and multifactorial, modulated by genetic and environmental determinants. During the last years, the hepatic disease has been progressively established from early stages in life. The use of genetic risk scores (GRS) to predict the genetic susceptibility to a particular phenotype among youth has gained interest in recent years. Moreover, the alanine aminotransferase (ALT) blood biomarker is often considered as hepatic screening tool, in combination with imaging techniques. The aim of the present study was to develop an ALT-specific GRS to help in the evaluation of hepatic damage risk in European adolescents. Methods: A total of 972 adolescents (51.3% females), aged 12.5¿17.5 years, from the Healthy Lifestyle in Europe by Nutrition in Adolescence study were included in the analyses. The sample incorporated adolescents in all body mass index (BMI) categories and was divided considering healthy/unhealthy ALT levels, using sex-specific cut-off points. From 1212 a priori ALT-related single nucleotide polymorphisms (SNPs) extracted from candidate gene selection, a first screening of 234 SNPs univariately associated was established, selecting seven significant SNPs (p <.05) in the multivariate model. An unweighted GRS (uGRS) was developed by summing the number of reference alleles, and a weighted GRS (wGRS), by multiplying each allele to its estimated coefficient. Results: The uGRS and wGRS were significantly associated with ALT (p <.001). The area under curve was obtained integrating BMI as clinical factor, improving the predictive ability for uGRS (.7039) and wGRS (.7035), using 10-fold internal cross-validation. Conclusions: Considering BMI status, both GRSs could contribute as complementary tools to help in the early diagnosis of hepatic damage risk in European adolescents.
Open Access
Interaction effect of the Mediterranean diet and an obesity genetic risk score on adiposity and metabolic syndrome in adolescents: the HELENA study
(MDPI, 2020) Seral-Cortes, Miguel; Sabroso-Lasa, Sergio; Miguel Etayo, Carmen de; González Gross, Marcela; Gesteiro, Eva; Molina Hidalgo, Cristina; Henauw, Stefaan de; Erhardt, Éva; Manios, Yannis; Karaglani, Eva; Widhalm, Kurt; Kafatos, Antonios; Béghin, Laurent; Meirhaeghe, Aline; Salazar-Tortosa, Diego; Ruiz, Jonatan R.; Moreno, Luis A.; Esteban, Luis Mariano; Labayen Goñi, Idoia; Ciencias de la Salud; Osasun Zientziak
Obesity and metabolic syndrome (MetS) are worldwide major health challenges. The Mediterranean diet (MD) is associated with a better cardiometabolic profile, but these beneficial effects may be influenced by genetic variations, modulating the predisposition to obesity or MetS. The aim was to assess whether interaction effects occur between an obesity genetic risk score (obesity-GRS) and the MD on adiposity and MetS in European adolescents. Multiple linear regression models were used to assess the interaction effects of an obesity-GRS and the MD on adiposity and MetS and its components. Interaction effects between the MD on adiposity and MetS were observed in both sex groups (p < 0.05). However, those interaction effects were only expressed in a certain number of adolescents, when a limited number of risk alleles were present. Regarding adiposity, a total of 51.1% males and 98.7% females had lower body mass index (BMI) as a result of higher MD adherence. Concerning MetS, only 9.9% of males with higher MD adherence had lower MetS scores. However, the same effect was observed in 95.2% of females. In conclusion, obesity-related genotypes could modulate the relationship between MD adherence and adiposity and MetS in European adolescents; the interaction effect was higher in females than in males.
Open Access
Association between CNTF polymorphisms and adiposity markers in European adolescents
(Mosby/Elsevier, 2020) Pascual Gamarra, José Miguel; Salazar-Tortosa, Diego; Labayen Goñi, Idoia; Rupérez, Azahara I.; Censi, Laura; Béghin, Laurent; Michels, Nathalie; González Gross, Marcela; Manios, Yannis; Lambrinou, Christina-Paulina; Moreno, Luis A.; Meirhaeghe, Aline; Castillo, Manuel J.; Ruiz, Jonatan R.; Ciencias de la Salud; Osasun Zientziak
Objective: To examine the association between polymorphisms of the ciliary neurotrophic factor gene (CNTF) and total and central adiposity markers in adolescents. Study design: This cross-sectional study involved 1057 European adolescents aged 12-18 years enrolled in the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study. Five polymorphisms of CNTF were genotyped, and the weight, height, waist and hip circumference, and triceps and subscapular skinfold thickness of the subjects were measured and recorded. Results: The T allele of rs2509914, the C allele of rs2515363, and the G allele of rs2515362 were significantly associated (after Bonferroni correction) with higher values for several adiposity markers under different inheritance models. The CNTF CCGGA haplotype (rs2509914, rs17489568, rs2515363 rs1800169, and rs2515362) was also significantly associated with lower body mass index, waist circumference, waist/height ratio, and waist/hip ratio values compared with the TCCGG haplotype under several inheritance models. Conclusions: Three polymorphisms—rs2509914, rs2515363, and rs2515362—and the CCGGA haplotype of CNTF were significantly associated with adiposity in European adolescents. These results suggest the potential role of CTNF in the development of obesity-related phenotypes.
Open Access
Single nucleotide polymorphisms of ADIPOQ gene associated with cardiovascular disease risk factors in European adolescents: the HELENA study
(Wolters Kluwer, 2020) Salazar-Tortosa, Diego; Pascual Gamarra, José Miguel; Labayen Goñi, Idoia; Rupérez, Azahara I.; Censi, Laura; Béghin, Laurent; Michels, Nathalie; González Gross, Marcela; Manios, Yannis; Lambrinou, Christina-Paulina; Moreno, Luis A.; Meirhaeghe, Aline; Castillo, Manuel J.; Ruiz, Jonatan R.; Ciencias de la Salud; Osasun Zientziak
Objectives: Cardiovascular diseases (CVDs) are responsible of 31% of all deaths worldwide. Genetic predisposition to CVDs in adolescents remains largely unknown. Aims of present research are to examine the association of ADIPOQ gene polymorphisms with cardiovascular disease risk factors in European adolescents. Methods: A total of 14 polymorphisms in the ADIPOQ gene were genotyped in 1057 European adolescents (12-18 years old) from the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study. We measured serum lipids and a CVD risk score, along with weight, height, triceps, and subscapular skinfold thickness, leptin, insulin and other markers of glucose regulation. Results: The rs822393, rs822395 and rs7649121 polymorphisms of ADIPOQ gene were significantly associated with several CVD risk factors [i.e. high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) A1, SBP and CVD risk score] in European adolescents. We also found an association of the TGAAGT ADIPOQ haplotype (rs822393, rs16861210, rs822395, rs822396, rs12495941 and rs7649121) with HDL-C and ApoA1 levels. Conclusion: Several individual polymorphisms (rs822393, rs822395 and rs7649121) and a haplotype of ADIPOQ gene were significantly associated with cardiovascular disease risk factors in European adolescents.
Open Access
Development of a genetic risk score to predict the risk of hypertension in european adolescents from the HELENA study
(Frontiers Media, 2023) Pérez-Gimeno, Gloria; Seral-Cortes, Miguel; Sabroso-Lasa, Sergio; Esteban, Luis Mariano; Lurbe, Empar; Béghin, Laurent; Gottrand, Frédéric; Meirhaeghe, Aline; Muntaner, Manon; Kafatos, Antonios; Molnár, Dénes; Leclercq, Catherine; Widhalm, Kurt; Kersting, Mathilde; Nova, Esther; Salazar-Tortosa, Diego; González Gross, Marcela; Breidenassel, Christina; Sinningen, Kathrin; Ruyter, Thaïs de; Labayen Goñi, Idoia; Rupérez, Azahara I.; Bueno-Lozano, Gloria; Moreno, Luis A.; Ciencias de la Salud; Osasun Zientziak; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD
Introduction: From genome wide association study (GWAS) a large number of single nucleotide polymorphisms (SNPs) have previously been associated with blood pressure (BP) levels. A combination of SNPs, forming a genetic risk score (GRS) could be considered as a useful genetic tool to identify individuals at risk of developing hypertension from early stages in life. Therefore, the aim of our study was to build a GRS being able to predict the genetic predisposition to hypertension (HTN) in European adolescents. Methods: Data were extracted from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study. A total of 869 adolescents (53% female), aged 12.5–17.5, with complete genetic and BP information were included. The sample was divided into altered (≥130 mmHg for systolic and/or ≥80 mmHg for diastolic) or normal BP. Based on the literature, a total of 1.534 SNPs from 57 candidate genes related with BP were selected from the HELENA GWAS database. Results: From 1,534 SNPs available, An initial screening of SNPs univariately associated with HTN (p < 0.10) was established, to finally obtain a number of 16 SNPs significantly associated with HTN (p < 0.05) in the multivariate model. The unweighted GRS (uGRS) and weighted GRS (wGRS) were estimated. To validate the GRSs, the area under the curve (AUC) was explored using ten-fold internal cross-validation for uGRS (0.802) and wGRS (0.777). Further covariates of interest were added to the analyses, obtaining a higher predictive ability (AUC values of uGRS: 0.879; wGRS: 0.881 for BMI z-score). Furthermore, the differences between AUCs obtained with and without the addition of covariates were statistically significant (p < 0.05). Conclusions: Both GRSs, the uGRS and wGRS, could be useful to evaluate the predisposition to hypertension in European adolescents.