Browsing by Author "Pereira, Ana"

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    A Polygenic Risk Score Suggests Shared Genetic Architecture of Voice Break With Early Markers of Pubertal Onset in Boys
    (2020) Lardone, María C.; Busch, Alexander S.; Santos Martín, José Luis; Miranda, José Patricio; Eyheramendy Duerr, Susana; Pereira, Ana; Juul, Anders; Almstrup, Kristian; Mericq, Verónica; José Patricio, Miranda
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    Association between indicators of systemic inflammation biomarkers during puberty with breast density and onset of menarche
    (2020) Michels, Karin B.; Santos Martín, José Luis; Keller, Kristen; Pereira, Ana; Kim, Claire E.; Shepherd, John A.; Corvalán, Camila; Binder, Alexandra M.
    Abstract Background Systemic inflammation may play a role in shaping breast composition, one of the strongest risk factors for breast cancer. Pubertal development presents a critical window of breast tissue susceptibility to exogenous and endogenous factors, including pro-inflammatory markers. However, little is known about the role of systemic inflammation on adolescent breast composition and pubertal development among girls. Methods We investigated associations between circulating levels of inflammatory markers (e.g., interleukin-6 (IL-6), tumor necrosis factor receptor 2 (TNFR2), and C-reactive protein (CRP)) at Tanner stages 2 and 4 and breast composition at Tanner stage 4 in a cohort of 397 adolescent girls in Santiago, Chile (Growth and Obesity Cohort Study, 2006–2018). Multivariable linear models were used to examine the association between breast composition and each inflammatory marker, stratifying by Tanner stage at inflammatory marker measurement. Accelerated failure time models were used to evaluate the association between inflammatory markers concentrations at each Tanner stage and time to menarche. Results In age-adjusted linear regression models, a doubling of TNFR2 at Tanner 2 was associated with a 26% (95% CI 7–48%) increase in total breast volume at Tanner 4 and a 22% (95% CI 10–32%) decrease of fibroglandular volume at Tanner 4. In multivariable models further adjusted for body fatness and other covariates, these associations were attenuated to the null. The time to menarche was 3% (95% CI 1–5%) shorter among those in the highest quartile of IL-6 at Tanner 2 relative to those in the lowest quartile in fully adjusted models. Compared to those in the lowest quartile of CRP at Tanner 4, those in the highest quartile experienced 2% (95% CI 0–3%) longer time to menarche in multivariable models. Conclusions Systemic inflammation during puberty was not associated with breast volume or breast density at the conclusion of breast development among pubertal girls after adjusting for body fatness; however, these circulating inflammation biomarkers, specifically CRP and IL-6, may affect the timing of menarche onset.Abstract Background Systemic inflammation may play a role in shaping breast composition, one of the strongest risk factors for breast cancer. Pubertal development presents a critical window of breast tissue susceptibility to exogenous and endogenous factors, including pro-inflammatory markers. However, little is known about the role of systemic inflammation on adolescent breast composition and pubertal development among girls. Methods We investigated associations between circulating levels of inflammatory markers (e.g., interleukin-6 (IL-6), tumor necrosis factor receptor 2 (TNFR2), and C-reactive protein (CRP)) at Tanner stages 2 and 4 and breast composition at Tanner stage 4 in a cohort of 397 adolescent girls in Santiago, Chile (Growth and Obesity Cohort Study, 2006–2018). Multivariable linear models were used to examine the association between breast composition and each inflammatory marker, stratifying by Tanner stage at inflammatory marker measurement. Accelerated failure time models were used to evaluate the association between inflammatory markers concentrations at each Tanner stage and time to menarche. Results In age-adjusted linear regression models, a doubling of TNFR2 at Tanner 2 was associated with a 26% (95% CI 7–48%) increase in total breast volume at Tanner 4 and a 22% (95% CI 10–32%) decrease of fibroglandular volume at Tanner 4. In multivariable models further adjusted for body fatness and other covariates, these associations were attenuated to the null. The time to menarche was 3% (95% CI 1–5%) shorter among those in the highest quartile of IL-6 at Tanner 2 relative to those in the lowest quartile in fully adjusted models. Compared to those in the lowest quartile of CRP at Tanner 4, those in the highest quartile experienced 2% (95% CI 0–3%) longer time to menarche in multivariable models. Conclusions Systemic inflammation during puberty was not associated with breast volume or breast density at the conclusion of breast development among pubertal girls after adjusting for body fatness; however, these circulating inflammation biomarkers, specifically CRP and IL-6, may affect the timing of menarche onset.
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    Association between plasma leptin/adiponectin ratio and insulin resistance indexes in prepubertal children
    (2024) Bravo, Carolina; Mericq, Verónica; Pereira, Ana; Corvalán, Camila; Tobar, Hugo E.; Miranda, José Patricio; Santos, José Luis
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    Breast bud detection: a validation study in the Chilean Growth Obesity Cohort Study
    (2014) Pereira, Ana; Garmendia, María, Luisa; González, Daniela; Kain, Juliana; Mericq, Verónica; Uauy, Ricardo; Corvalán, Camila
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    Correction to: Novel loci and mapuche genetic ancestry are associated with pubertal growth traits in Chilean boys (Human Genetics, (2021), 10.1007/s00439-021-02290-3)
    (Springer Science and Business Media Deutschland GmbH, 2021) Vicuña, Lucas; Norambuena, Tomás; Miranda, José Patricio; Eyheramendy, Susana; Pereira, Ana; Mericq, Verónica; Ongaro, Linda; Montinaro, Francesco; Lorenzoni Santos, José Guillermo
    © 2021, Springer-Verlag GmbH Germany, part of Springer Nature.Several typos were introduced in the original article and they have been corrected. The original article has been revised.
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    Dairy intake in relation to breast and pubertal development in Chilean girls
    (2017) Gaskins, Audrey J.; Pereira, Ana; Quintiliano, Daiana; Shepherd, John A.; Uauy, Ricardo; Corvalán, Camila; Michels, Karin B.
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    Differential methylation pattern in pubertal girls associated with biochemical premature adrenarche
    (2023) Ponce, Diana; Rodríguez, Fernando; Miranda, José P.; Binder, Alexandra M.; Santos, José L.; Michels, Karin B.; Cutler, Gordon B.; Pereira, Ana; Iñiguez, Germán; Mericq, Verónica
    Biochemical premature adrenarche is defined by elevated serum DHEAS [≥40 μg/dL] before age 8 y in girls. This condition is receiving more attention due to its association with obesity, hyper-insulinemia, dyslipidemia, and polycystic ovary syndrome. Nevertheless, the link between early androgen excess and these risk factors remains unknown. Epigenetic modifications, and specifi-cally DNA methylation, have been associated with the initiation and progression of numerous disorders, including obesity and insulin resistance. The aim of this study was to determine if prepubertal androgen exposure is associated with a different methylation profile in pubertal girls. Eighty-six healthy girls were studied. At age 7 y, anthropometric measurements were begun and DHEAS levels were determined. Girls were classified into Low DHEAS (LD) [<42 μg/dL] and High DHEAS (HD) [≥42 μg/dL] groups. At Tanner stages 2 and 4 a DNA methylation microarray was performed to identify differentially methylated CpG positions (DMPs) between HD and LD groups. We observed a differential methylation pattern between pubertal girls with and without bio-chemical PA. Moreover, a set of DNA methylation markers, selected by the LASSO method, successfully distinguished between HD and LD girls regardless of Tanner stage. Additionally, a subset of these markers were significantly associated with glucose-related measures such as insulin level, HOMA-IR, and glycaemia. This pilot study provides evidence consistent with the hypothesis that high DHEAS concentration, or its hormonally active metabolites, may induce a unique blood methylation signature in pubertal girls, and that this methylation pattern is associated with altered glucose metabolism.
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    Early Obesity: Risk Factor for Fatty Liver Disease
    (LIPPINCOTT WILLIAMS & WILKINS, 2020) Cuzmar, Valeriau; Alberti, Gigliola; Uauy, Ricardo; Pereira, Ana; Garcia, Cristian; De Barbieri, Florencia; Corvalan, Camila; Santos, Jose L.; Mericq, Veronica; Villarroel, Luis; Gana, Juan Cristobal
    Nonalcoholic fatty liver disease (NAFLD), defined as fat accumulation greater than 5% in hepatocytes, may progress to fibrosis or cirrhosis later in life. NAFLD prevalence in adolescents has increased significantly in direct relation with obesity prevalence. Fatty liver has become the most frequent indication for liver transplantation in adults. Objective: The aim of the study was to identify anthropometric variables during the first 10 years of life associated to the risk of developing NAFLD in adolescence. Methods: Longitudinal cohort study 'Growth and Obesity Chilean Cohort Study' (GOCS) consisting of 513 children born in 2002 to 2003, with yearly anthropometric data collected over a 10-year period. The presence of intrahepatic fat in the livers of subjects 14 to 16 years of age was determined using abdominal ultrasound. In addition, elastography was performed on all participants with ultrasound evidence of NAFLD. Results: 9.7% of the participants presented findings compatible with NAFLD. After 2 years of age, obesity significantly and progressively increased the probability of NAFLD occurrence in adolescence. Obesity at 5 years of age was associated with the highest OR for NAFLD, reaching values of 8.91 (95% CI 3.03-16.11). Among participants with NAFLD, those with altered liver elasticity (>= 7 kPa) had greater weight, BMIz-score, waist and hip circumference, and altered liver enzymes (P < 0.05). Conclusion: The risk of developing NAFLD in adolescence increases progressively with early obesity starting at age 2 years.
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    Faster ticking rate of the epigenetic clock is associated with faster pubertal development in girls
    (2018) Binder, Alexandra M.; Corválan, Camila; Mericq, Verónica; Pereira, Ana; Santos Martín, José Luis; Horvath, Steve; Shepherd, John; Michels, Karin B.
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    Genetic determinants of serum bilirubin using inferred native American gene variants in Chilean adolescents
    (2024) Miranda Marín, José Patricio; Pereira, Ana; Corvalán, Camila; Miquel P., Juan Francisco; Alberti, Gigliola; Gana Ansaldo, Juan Cristóbal; Santos Martín, José Luis
    Gene variants in the UGT1A1 gene are strongly associated with circulating bilirubin levels in several populations, as well as other variants of modest effect across the genome. However, the effects of such variants are unknown regarding the Native American ancestry of the admixed Latino population. Our objective was to assess the Native American genetic determinants of serum bilirubin in Chilean admixed adolescents using the local ancestry deconvolution approach. We measured total serum bilirubin levels in 707 adolescents of the Chilean Growth and Obesity Cohort Study (GOCS) and performed high-density genotyping using the Illumina-MEGA array (>1.7 million genotypes). We constructed a local ancestry reference panel with participants from the 1000 Genomes Project, the Human Genome Diversity Project, and our GOCS cohort. Then, we inferred and isolated haplotype tracts of Native American, European, or African origin to perform genome-wide association studies. In the whole cohort, the rs887829 variant and others near UGT1A1 were the unique signals achieving genome-wide statistical significance (b = 0.30; p = 3.34 × 10−57). After applying deconvolution methods, we found that significance is also maintained in Native American (b = 0.35; p = 3.29 × 10−17) and European (b = 0.28; p = 1.14 × 10−23) ancestry components. The rs887829 variant explained a higher percentage of the variance of bilirubin in the Native American (37.6%) compared to European ancestry (28.4%). In Native American ancestry, carriers of the TT genotype of this variant averaged 4-fold higher bilirubinemia compared to the CC genotype (p = 2.82 × 10−12). We showed for the first time that UGT1A1 variants are the primary determinant of bilirubin levels in Native American ancestry, confirming its pan-ethnic relevance. Our study illustrates the general value of the local ancestry deconvolution approach to assessing isolated ancestry effects in admixed populations.
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    High DHEAS in girls and metabolic features throughout pubertal maturation
    (2022) Pereira, Ana; Merino, Paulina M.; Santos, Jose L.; Iñiguez, German; Cutler, Gordon B.; Corvalan, Camila; Mericq, Veronica
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    High-speed resistance training is more effective than low-speed resistance training to increase functional capacity and muscle performance in older women
    (2014) Ramírez-Campillo, Rodrigo; Castillo, Angélica; De la Fuente, Carlos; Campos Jara, Christian Alex; Andrade Andrade, David Cristóbal; Álvarez, Cristian; Martínez Belmar, Cristian Antonio; Castro Sepúlveda, Mauricio; Pereira, Ana; Marques, Mário C.; Izquierdo, Mikel
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    New insights from GWAS on BMI-related growth traits in a longitudinal cohort of admixed children with Native American and European ancestry
    (CELL PRESS, 2023) Vicuña, Lucas; Barrientos, Esteban; Norambuena, Tomás; Alvares, Danilo; Gana Ansaldo, Juan Cristóbal; Leiva Yamaguchi, Valeria; Meza, Cristian; Lorenzoni Santos, José Guillermo; Mericq, Verónica; Pereira, Ana; Eyheramendy, Susana
    Body-mass index (BMI) is a hallmark of adiposity. In contrast with adulthood, the genetic architecture of BMI during childhood is poorly understood. The few genome-wide association studies (GWAS) on children have been performed almost exclusively in Europeans and at single ages. We performed cross-sectional and longitudinal GWAS for BMI-related traits on 904 admixed children with mostly Mapuche Native American and European ancestries. We found regulatory variants of the immune gene HLA-DQB3 strongly associated with BMI at 1.5 - 2.5 years old. A variant in the sex-determining gene DMRT1 was associated with the age at adiposity rebound (Age-AR) in girls (P = 9.8 x 10(-9)). BMI was significantly higher in Mapuche than in Europeans between 5.5 and 16.5 years old. Finally, Age-AR was significantly lower (P = 0.004) by 1.94 years and BMI at AR was significantly higher (P = 0.04) by 1.2 kg/m(2), in Mapuche children compared with Europeans.
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    Relation between body composition trajectories from childhood to adolescence and nonalcoholic fatty liver disease risk
    (2024) Alberti, Gigliola; Faune Palacios, Mariana Carmen; Santos Martín, José Luis; De Barbieri Magnone, Florencia Beatriz; García B., Cristián; Pereira, Ana; Becerra, Fernando; Gana Ansaldo, Juan Cristóbal
    NAFLD has become the leading cause of chronic liver disease in children, as a direct consequence of the high prevalence of childhood obesity. This study aimed to characterize body composition trajectories from childhood to adolescence and their association with the risk of developing nonalcoholic fatty liver disease (NAFLD) during adolescence. The participants were part of the ‘Chilean Growth and Obesity Cohort Study’, comprising 784 children who were followed prospectively from age 3 years. Annual assessments of nutritional status and body composition were conducted, with ultrasound screening for NAFLD during adolescence revealing a 9.8% prevalence. Higher waist circumference measures were associated with NAFLD from age 3 years (p = 0.03), all skin folds from age 4 years (p < 0.01), and DXA body fat measurements from age 12 years (p = 0.01). The fat-free mass index was higher in females (p = 0.006) but not in males (p = 0.211). The second and third tertiles of the fat mass index (FMI) had odds ratios for NAFLD during adolescence of 2.19 (1.48–3.25, 95% CI) and 6.94 (4.79–10.04, 95% CI), respectively. Elevated waist circumference, skin folds, and total body fat were identified as risk factors for future NAFLD development. A higher FMI during childhood was associated with an increased risk of NAFLD during adolescence.
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    Ultrasensitive estrogen levels at 7 years of age predict earlier thelarche : evidence from girls of the growth and obesity Chilean cohort
    (2015) Pereira, Ana; Corvalán, Camila; Uauy, Ricardo; Klein, Karen O.; Mericq, Verónica