Asociación entre el polimorfismo rs9939609 del gen FTO y marcadores de adiposidad en población infantil chilena / Association between FTO gene rs9939609 and adiposity markers in Chilean children

Resumen: Introducción: La obesidad es una enfermedad inflamatoria donde la genética determina cierto nivel de riesgo. Aun cuando existen estudios que reportan asociación entre polimorfismos de FTO (fat-mass associated gene) y adiposidad, existe limitada evidencia en población infantil chilena. Objetivo: determinar la asociación entre el polimorfismo rs9939609 del FTO y marcadores de adiposidad en población in fantil chilena. Pacientes y Método: Estudio de corte transversal incluyó 361 participantes (de 6 a 11 años; 50% niñas). Los datos clínicos y la recolección de muestras de sangre se realizaron entre marzo y junio de 2008. El polimorfismo SNP (rs9939609), del gen FTO, se determinó utilizando ADN genómico extraído de leucocitos, utilizando el Mini Kit QIAamp DNA Blood (Qiagen GmbH, Hilden, Alemania). Los marcadores de adiposidad estudiados fueron, índice de masa corporal (IMC), masa grasa, perímetro de cintura (PC) y razón cintura/talla, y se compararon ajustados por sexo, edad y estadio de Tanner. La asociación entre el polimorfismo estudiado y los marcadores de obesidad se realizó mediante análisis de regresión lineal. Resultados: Al ajustar los marcadores por sexo, edad y estadío de Tanner se observó una asociación significativa entre el polimorfismo e indicadores de adi posidad. Por cada copia extra del alelo de riesgo se encontró un aumento de 2,47 kg de peso corporal, (IC 95%: 1,39-3,55); 1,06 kg/m2 de IMC, (IC 95%: 0,56-1,54); 2,55 cm de PC, (IC 95%: 1,26-3,85) y 1,98% de masa grasa, (IC 95%: 0,78-3,19). Al convertir los marcadores de adiposidad a z-score, la razón perímetro de cintura/talla arrojó la mayor asociación con el alelo de riesgo de FTO. Conclu sión: Este estudio indica asociación entre el polimorfismo rs9939609 del gen FTO con marcadores de adiposidad general y central en población infantil en Chile.

Abstract: Introduction: Obesity is considered a chronic inflammatory disease with an important genetic component. Although several studies have reported an association between the FTO (fat-mass associated gene) and adiposity in children, there is limited evidence in the Chilean population. Objective: To deter mine the association between the polymorphism rs9939609 of the FTO gene and markers of adipo sity in Chilean children. Patients and Method: Cross-sectional study which included 361 children aged between 6 and 11 years (50% were girls). Between March and June 2008, clinical data and blood sample collection was carried out. The rs9939609 single-nucleotide polymorphism (SNP) of the FTO gene, was determined using the genomic DNA extracted from leukocytes, using the QIAamp DNA Blood Mini Kit (Qiagen GmbH, Hilden, Germany).The adiposity markers included were body mass index (BMI), waist circumference (WC), body fat, and WC/H index; which were later compared adjusted by sex, age, and Tanner stage. Linear regression analyses were conducted to detect the association between the polymorphism and obesity markers. Results: After adjusting the models by age, sex, and Tanner stage, we found a significant association between the polymorphism and markers of adiposity. For each extra copy of the risk allele, we found an increase of 2.47 kg body weight (95% CI: 1.39-3.55); 1.06 kg/m2 BMI (95% CI: 0.56-1.54); 2.55 cm WC, (95% CI: 1.26-3.85); and 1.98% body fat (95% CI: 0.78-3.19). When converting adiposity markers to z-score, we found that WC/height index shows the strongest association with the risk allele FTO. Conclusion: This study supports the association between the rs9939609 SNP of the FTO gene and overall and central adiposity markers in Chilean children.

Efecto del estado nutricional neonatal en la asociación entre polimorfismo rs9939609 del gen FTO y obesidad en niños chilenos de origen amerindio / Effects of neonatal undernutrition on the association of obesity with rs9939609 polymorphism of FTO gene among Amerindian children

The presence of A allele in FTO gene is associated with a higher risk of obesity. Aim: to investigate the effect of neonatal nutritional status on the association between FTO gene rs9939609 variant and obesity in a cohort of Chilean children with Amerindian ancestry. Material and Methods: using birth registries, the neonatal ponderal index of 238 obese and 136 normal weight children was calculated. Nutritional status of participants was determined using cutoff points proposed by the Center for Disease Control. FTO polymorphism was measured by real time polymerase chain reaction. Results: the presence of FTO A allele was associated with a higher risk of obesity (odds ratio (OR) 1.87 95 percent confidence intervals (CI) 1.14-3.06, p < 0.01). The effect of this allele was only significant among males. The risk of obesity associated with A allele presence was non-significantly higher among males with a neonatal ponderal index below percentile 10, as compared with their counterparts with a neonatal ponderal index above this value (OR 5.65 95 percent CI 0.87-60.4). A logistic regression analyzing the presence of A allele as a risk factor for obesity using neonatal nutritional status and gender as control variables, did not substantially change the results. Conclusions: there is a non-significant effect of neonatal undernutrition on the risk of obesity conferred by the presence of A allele of FTO gene...

Asociación entre polimorfismos del gen de adiponectina y estado nutricional en escolares de la comuna de Hualpén / Association between adiponectin gene polymorphisms and obesity in school age children from Hualpén, Chile

Background: Several genetic polymorphisms of adiponectin have been associated to metabolic diseases as obesity and co-morbidities. Aim: To investigate if there are associations between +45TG, +276GT, -11,377CG y -11,391GA adiponectin SNPs (single nucleotide polymorphism) with obesity in a Chilean children population. Material and Methods: A case-control study was performed in 241 obese and 126 normal weight children (7-11 years old) from the urban community of Hualpén, Biobío region. Children were classified as normal or obese, according to age and gender-specificpercentiles defined by Centerfor Disease Control and Prevention (CDC). The analysis of serum markers was carried out using commercial kits. Adiponectin polymorphisms were determined through a High Resolution Melting (HRM)-enabled real time PCR and by DNA fragment sequencing. Results: The observed allelic frequencies of the studied SNPs were over 11%. The 11,377CG polymorphism was associated with a high risk of obesity, calculated by the additive inheritance model (odds ratio = 1.389, 95% confidence interval: 1.001-1.929,p = 0.049). Conclusions: Obese school children of the Biobío Region, have an increased risk of carrying the susceptibility allele polymorphism 11377CG of adiponectin gene.