Association between the FTO SNP rs9939609 and Metabolic Syndrome in Chilean Children.

BACKGROUND: The increasing prevalence of obesity in children has raised the incidence of Metabolic Syndrome (MetS) in this age group. Given the short- and long-term health impact of MetS, it is essential to prevent its onset by detecting its main triggers. Besides, genetic factors play an essential role in influencing which individuals within a population are most likely to develop obesity in response to a particular environment. In this regard, a common variation in the FTO gene is reproducibly associated with BMI and obesity from childhood and the genetic load has been linked to several cardiovascular risk factors, highlighting the FTO single nucleotide polymorphism (SNP) rs9939609. Therefore, this study aimed to establish the relationship between the FTO SNP rs9939609 and MetS. METHODS: A cross-sectional study was carried out on 220 children from the Biobío region (Chile). MetS diagnosis was established through the modified Cook criteria, using prevalence ratios, COR curves, and linear regressions to determine its association with MetS and its components. RESULTS: The prevalence of MetS was significantly increased among carriers of the risk allele (A): TT, 20.2%; TA, 25.4%; AA, 44.7% (p = 0.006). Also, the presence of A was associated with altered MetS-related variables. CONCLUSIONS: The FTO SNP rs9939609 was associated with a raised prevalence of MetS among A allele carriers, and was higher in the homozygous genotype (AA).

An Approach to Early Detection of Metabolic Syndrome through Non-Invasive Methods in Obese Children.

BACKGROUND: Metabolic Syndrome (MetS) has a high prevalence in children, and its presence increases in those with a high BMI. This fact confirms the need for early detection to avoid the development of other comorbidities. Non-invasive variables are presented as a cost-effective and easy to apply alternative in any clinical setting. AIM: To propose a non-invasive method for the early diagnosis of MetS in overweight and obese Chilean children. METHODS: We conducted a cross-sectional study on 221 children aged 6 to 11 years. We carried out multivariate logistic regressions, receiver operating characteristic curves, and discriminant analysis to determine the predictive capacity of non-invasive variables. The proposed new method for early detection of MetS is based on clinical decision trees. RESULTS: The prevalence of MetS was 26.7%. The area under the curve for the BMI and waist circumference was 0.827 and 0.808, respectively. Two decision trees were calculated: the first included blood pressure (≥104.5/69 mmHg), BMI (≥23.5 Kg/m2) and WHtR (≥0.55); the second used BMI (≥23.5 Kg/m2) and WHtR (≥0.55), with validity index of 74.7% and 80.5%, respectively. CONCLUSIONS: Early detection of MetS is possible through non-invasive methods in overweight and obese children. Two models (Clinical decision trees) based on anthropometric (non-invasive) variables with acceptable validity indexes have been presented. Clinical decision trees can be applied in different clinical and non-clinical settings, adapting to the tools available, being an economical and easy to measurement option. These methods reduce the use of blood tests to those patients who require confirmation.

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

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.

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.

Hypogonadotropic Hypogonadism and Short Stature in Patients with Diabetes Due to Neurogenin 3 Deficiency.

CONTEXT: Biallelic mutations in NEUROG3 are known to cause early-onset malabsorptive diarrhea due to congenital anendocrinosis and diabetes mellitus at a variable age. No other endocrine disorders have been described so far. We report four patients with homozygous NEUROG3 mutations who presented with short stature and failed to show any signs of pubertal development. CASE DESCRIPTION: Four patients (two males, two females) were diagnosed with homozygous mutations in NEUROG3 on the basis of congenital malabsorptive diarrhea and diabetes. All four had severe short stature and failed to develop secondary sexual characteristics at an appropriate age, despite some having normal body mass index. The absence of gonadal function persisted into the third decade in one patient. Upon testing, both basal and stimulated LH and FSH levels were low, with the remaining pituitary hormones within the normal range. Magnetic resonance imaging scans of the hypothalamic-pituitary axis did not reveal structural abnormalities. A diagnosis of hypogonadotropic hypogonadism was made, and replacement therapy with sex hormones was started. CONCLUSIONS: The high reproducibility of this novel phenotype suggests that central hypogonadism and short stature are common findings in patients with mutations in NEUROG3. Growth rate needs to be carefully monitored in these patients, who also should be routinely screened for hypogonadism when they reach the appropriate age. NEUROG3 mutations expand on the growing number of genetic causes of acquired hypogonadotropic hypogonadism.

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.

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

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.

Metabolic syndrome in obese adolescents.

Childhood and adolescent obesity is highly prevalent and a relevant public health problem in Chile. Metabolic syndrome (MS), which is predictive of future cardiovascular disease and type 2 diabetes, has been associated with childhood obesity and insulin resistance. The aim of this study was to determine the prevalence of MS in a non-consultant obese adolescent population and to assess the underlying factors for the MS in these subjects. The nutritional status was evaluated for 25,102 students from 10 to 18 years of age living in Concepcin and Coronel, Chile. A total of 2,308 adolescents were found to be obese (BMI > or = 95 percentile). Metabolic syndrome was defined as the presence of at least three of the following abnormalities: waist circumference > or = 90th percentile, blood pressure > or= 90th percentile, fasting glycaemia > or = 100 mg/dL, HDL-cholesterol < or = 40 mg/dL and triglycerides > or = 110 mg/dL in a representative sample of 461 adolescents. The results obtained indicate that the prevalence of obesity was 9.2% and that MS reached 37.5%. Only 4.1% of the adolescents failed to present any of the risk factors for MS. When compared with the adolescents without MS, the estimated odd ratios (OR) for the presence of the characteristics of MS were all statistically significant, with increased waist circumference reaching an OR of 21.56. A significant difference was found between adolescents with and without MS; the parameters indicated greater insulin resistance for adolescents with MS. In conclusion, MS is highly prevalent among Chilean adolescents with obesity and its prevention beginning in childhood needs to be addressed.

Tobacco, alcohol, and illicit drug use in adolescents with diabetes mellitus.

BACKGROUND: Substance abuse in adolescents with diabetes mellitus (DM) is associated with the development of acute and chronic complications. OBJECTIVE: To determine the prevalence of alcohol, tobacco, and illicit drug consumption in adolescents with DM and compare it with the prevalence in a large contemporary control (C) group. METHODS: Adolescents with and without DM, who were attending 8th-12th grades, answered a structured written questionnaire, which evaluates the voluntary declaration of tobacco, alcohol, and illicit drug consumption. Subjects with DM were recruited from free diabetes camps or public hospitals (n = 193). The C group was obtained from a nationwide study of prevalence of substance abuse (n = 58,489). For illicit drugs (marijuana, cocaine, or cocaine sulfate), results are shown as life prevalence (ever used the substance). For alcohol and tobacco, results are shown as last month prevalence (the substance was used during the last month). RESULTS: Adolescents with DM showed a lower last month prevalence of tobacco and alcohol consumption than C (27.7 vs. 39.0%, p < 0.01 and 30.1 vs. 39.2%, p < 0.01, respectively). DM group had a lower life prevalence rate of illicit drugs than C group (9.6 vs. 22.2%, respectively; p < 0.01). A lower prevalence of tobacco, alcohol, and illicit drug use in DM group compared with C group was observed in grades 8, 9, and 10. However, a similar frequency of consumption was observed in 11th and 12th grades. CONCLUSION: Compared with healthy youth, DM patients use less tobacco, alcohol, and illicit drugs during the first years of adolescence but not later.

HLA non-class II genes may confer type I diabetes susceptibility in a Mapuche (Amerindian) affected family.

A rare case of type I diabetes is studied in an Amerindian (Mapuche) family from Chile, analyzing glutamic acid decarboxylase, islet-cell autoantibodies and human leukocyte antigen (HLA) genes. The affected sib is the only one that has one specific HLA haplotype combination that differs from the other sibs only in the HLA class I genes. It is concluded that HLA diabetes susceptibility factors may be placed outside the class II region or even that susceptibility factors do not exist in the HLA region in this Amerindian family.

[HLA genetic markers and auto-antibody profile in a Mapuche family with a case affected of type 1 diabetes]. / Marcadores genéticos (HLA) y perfil de auto-anticuerpos en una familia mapuche con un caso de diabetes tipo 1.

BACKGROUND: Type 1 diabetes (DM1) is caused by an autoimmune process that destroys beta cells of pancreas. Not all carriers of susceptible HLA genes and positive for autoantibodies develop the disease. Environmental factors play a role in triggering the autoimmune process. AIM: To analyze an exceptional case of DM1 in a Mapuche family in the context of genetic, immunological and environmental factors. SUBJECTS AND METHODS: A study of a family with an affected female child was carried out in a Mapuche community in Southern Chile (VIII region). This is an unique and sporadic DM1 case with Mapuche heritage. Nutritional and viral infections data were collected by interview and clinical records. A genetic analysis by PCR was done to detect class I and II HLA genes by reverse dot blot. RESULTS: The proband, her mother and sister had positive islet cell antibodies (ICA). Her father and brother were negative. All thefamily was positive for anti glutamic decarboxylase antibodies (GAD65). All subjects had HLA-DRB1 0407/0407 and HLA-DQB1 0302/0302 alleles. The index case and her father were homozygotes for the HLA-A1:A*68012/A*68012 allele. Mean breastfeeding lapse was 18 months in all children. No evidences for viral infections such as rubella, mumps or measles were found in this family. CONCLUSIONS: There was an altered profile of autoantibodies in the family of the index case. All genotypes were comparable with the European population where the diabetogenic combination DR4/DQB1*0302 is the most prevalent. No environmental factors could be incriminated as triggers of the disease.

Concentraciones plasmáticas normales de magnesio y calcio en madres y recién nacidos / Normal serum concentrations of magnesium and clacium in mothers and their newborn infants

Se determinaron los niveles plasmáticos de Mg y Ca en 22 madres y sus recién nacidos (RN). La concentración plasmática de Mg en las madres fue en promedio (x) = 1,78 ñ 0,23 mg x dl; el valor en el cordón del RN: x = 1,87 ñ 0,18 mg x dl y en el capilar del RN: x = 2,50 ñ 0,18 mg x dl. Este último valor fue significativamente mayor que los anteriores (p < 0,01). Las calcemias maternas obtenidas fueron en x = 10,56 ñ 0,67 mg x dl, valores significativamente menores (p < 0,01) que los valores del cordón del RN: x = 11,57 ñ 0,69 mg x dl y del capilar RN: x = 12,17 ñ 1,04 mg x dl. No encontramos correlación entre los valores de Ca y Mg en madres ni RN. Los valores de Ca y Mg obtenidos están dentro de los descritos por la literatura. Se demostró el valor del micrométodo como técnica útil en el período neonatal para determinar los niveles plasmáticos de Mg y Ca

Hipotiroidismo congénito: evaluación neurológica y sicométrica / Congenital hypothyroidism: neurologic and psichometric evaluation

Se analizan 22 niños portadores de HTC,cuyo diagnóstico se formula sobre bases clínicas y se confirma posteriormente por exámenes de laboratório. El 95% de los niños presenta alterciones neurológicas de intensidad variable, el 91% tiene un CI inferior al normal y el 59% de ellos necesita educación especial

Hiperinsulinismo en recién nacido / Hyperinsulinismo in a newborn infant

Se describen 2 pacientes, recién nacidos, con hipoglicemia secundaria a hiperinsulinemia. Se confirmó la hipersecreción de la hormona mediante radioinmunoanálisis en el plasma. Se extirpó 95% del tejido pancreático en ambos casos, lográndose el control de la hipoglicemia. Los dos pacientes tuvieron hiperglicemia transitoria en las primeras horas después de la operación, pero diez días más tarde sus insulinemias y glicemias eran normales y tres meses después mostraban desarrollos pondoestaturales y psicomotrices adecuados. El estudio histológidco preliminar reveló nesidioblastosis y leve componente de displasia endocrina en uno de los casos y displasia endocrina con leve componente de nesidioblastosis en el otro

Pericarditis y vasculitis secundarias a la administración de propiltiouracilo / Pericarditis and vasculitis secondary to the administration of propylthiouracil

Se describe un pacientes de 11 años de edad con bocio multinodular hipertiroídeo que después de 26 meses de tratamiento con Propiltiouracilo sufrió una reacción adversa con la droga, con evidencias de pericarditis, vasculitis y granulocitopenia. Los síntomas desaparecieron rápidamente al suspender la droga. Posteriormente fue sometido a tiroidectomía y tratamiento hormonal de reemplazo

Concentraciones plasmáticas de magnesio en lactantes con diarrea aguda, deshidratación y acidosis / Plasma concentrations of magnesium in infants with acute diarrhea, dehydration and acidosis

La concentración de Mg en el plasma de 22 lactantes sanos fue en promedio de 23,90 + ou - 1,63 mg x 1, similar a la de otras publicaciones. En 20 lactantes con diarrea aguda y deshidratación con o sin acidosis, las concentraciones plasmáticas fueron leve pero significativamente elevadas con respecto a los controles sanos, promedio 26,75 + ou - 3,49 mg x 1.(p <0,01)