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Background There is little information about familial hypercholesterolemia (FH) epidemiology and care in Ibero-American countries. The Ibero-American FH network aims at reducing the gap on diagnosis and treatment of this disease in the region. Objective To describe clinical, molecular, and organizational characteristics of FH diagnosis in Argentina, Brazil, Chile, Colombia, Mexico, Portugal, Spain, and Uruguay. Methods Descriptive analysis of country data related to FH cascade screening, molecular diagnosis, clinical practice guidelines, and patient organization presence in Ibero-America. Results From a conservative estimation of an FH prevalence of 1 of 500 individuals, there should be 1.2 million heterozygous FH individuals in Ibero-America and roughly 27,400 were diagnosed so far. Only Spain, Brazil, Portugal, and Uruguay have active cascade screening programs. The prevalence of cardiovascular disease ranged from 10% to 42% in member countries, and the highest molecular identification rates are seen in Spain, 8.3%, followed by Portugal, 3.8%, and Uruguay with 2.5%. In the 3 countries with more FH patients identified (Spain, Portugal, and Brazil) between 10 and 15 mutations are responsible for 30% to 47% of all FH cases. Spain and Portugal share 5 of the 10 most common mutations (4 in low density lipoprotein receptor [ LDLR ] and the APOB3527). Spain and Spanish-speaking Latin American countries share 6 of the most common LDLR mutations and the APOB3527. LDL apheresis is available only in Spain and Portugal and not all countries have specific FH diagnostic and treatment guidelines as well as patient organizations. Conclusions Ibero-American countries share similar mutations and gaps in FH care. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to investigate the allelic frequency of the fat mass and obesity-associated (FTO) gene (rs9939609) and its influences on obesity and metabolic risk biomarkers in a cohort of normal weight and obese Chilean children determining its ethnicity. Methods A total of 136 normal weight children and 238 obese children (between 6 and 11 yr old) from an urban setting were recruited for this case-control study. The children were classified as normal weight [body mass index (BMI) ≥ 5th and < 85th percentiles] or obese (BMI >95th percentile), according to the international age- and gender-specific percentiles defined by the Center for Disease Control and Prevention. The analysis of serum markers was carried out using commercial kits. The FTO polymorphism was determined through a high-resolution melting enabled real time polymerase chain reaction. Ethnicity was determined by analyzing mitochondrial DNA by the restriction fragment length polymorphism method. Results As much as 85% of the cohort was Amerindian. The minor A allele of rs9939609 was associated with obesity (odds ratio (OR): 1.422 [95% confidence interval (CI) 1.068-1.868] p = 0.015), calculated using an additive model. In sex-stratified analysis we found that the risk variant (A) of rs9939609 was associated with a higher homeostasis model of assessment for insulin (HOMA-IR) in prepubertal obese girls. In male carriers of the A allele, HOMA-IR showed no further deterioration than that already associated with obesity. Conclusions In summary, we confirm the association of the FTO gene single-nucleotide polymorphism rs9939609 with obesity in Chilean Amerindian children. Furthermore we show an association between the risk allele (A) and insulin resistance-related markers in prepubertal obese girls. [ABSTRACT FROM AUTHOR]

Bustos P, Saez K, Gleisner A, Ulloa N, Calvo C, Asenjo S. 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 ≥ 95 percentile). Metabolic syndrome was defined as the presence of at least three of the following abnormalities: waist circumference ≥ 90th percentile, blood pressure ≥ 90th percentile, fasting glycaemia ≥ 100 mg/dL, HDL-cholesterol ≤ 40 mg/dL and triglycerides ≥ 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. [ABSTRACT FROM AUTHOR]

Familial hypercholesterolemia (FH) is an inherited disorder mainly caused by mutations in the LDL receptor (LDL-R) and characterized by elevation of low-density lipoprotein cholesterol (LDL-C) levels and premature cardiovascular disease. In this study, we evaluated the clinical phenotype of the p.Asp47Asn, described as an uncertain pathogenic variant, and its effect on the structure of LDL-R and ligand interactions with apolipoproteins. 27 children and adolescents with suspected FH diagnosis were recruited from a pediatric endocrinology outpatient clinic. Blood samples were collected after 12 h fasting for lipid profile analysis. DNA sequencing was performed for six FH-related genes by Ion Torrent PGM platform and copy number variation by MLPA. For index cases, a familial cascade screening was done restricted to the same mutation found in the index case. In silico analysis were developed to evaluate the binding capacity of LDL-R to apolipoproteins B100 and E. Lipid profile in children and adolescents demonstrated higher LDL-C levels in p.Asp47Asn carriers compared to the wild type genotype. In silico analysis predicted a reduction in the binding capacity of the ligand-binding modules LA1-2 of p.Asp47Asn LDL-R for ApoB100 and ApoE, which was not produced by local structural changes or folding defects but as a consequence of a decreased apparent affinity for both apolipoproteins. The clinical phenotype and the structural effects of p.Asp47Asn LDL-R mutation suggest that this variant associates to FH. [Display omitted] • p.Asp47Asn carriers displayed higher LDL cholesterol levels than wild type. • In silico analysis predicted a lower affinity of LDL-R variant for apoB100 and apoE. • p.Asp47Asn associates to a clinical phenotype of Familial Hypercholesterolemia. [ABSTRACT FROM AUTHOR]

Background: Familial hypercholesterolemia (FH) is commonly associated with mutations in-LDL receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9)., Aim: To identify genetic variants associated with FH in a population of children and adolescents with hypercholesterolemia or a family history of-demonstrated early CVD., Material and Methods: Clinical and biochemical parameters were evaluated, and nine genes related to FH were sequenced namely LDLR, APOB, PCSK9, LDLRAP1, LIPA, APOE, ABCG5, ABCG8 and STAP1, in 55 children and adolescents aged 1 to 18 years old, from non-consanguineous families., Results: Mutations associated with FH were found in 17 children and adolescents, corresponding to p.Asp47Asn, duplication of exons 13-15 and p.Ser326Cys of the LDLR gene; p.Glu204* and Ile268Met of the APOE gene. Thirteen patients were heterozygous, two homozygous, two compound heterozygous, and one double heterozygous., Conclusions: Children and adolescents carrying mutations associated with FH were found by selective screening, which constitutes the first stage in the identification of genetic variants in our country.

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.

Background: The frequency of obesity is increasing steadily in Chile., Aim: To assess the prevalence of obesity and overweight in children and teenagers living in three southern Chilean cities., Material and Methods: The database of an evaluation performed in 2006 in schools, was used to obtain weight and height of 32514 subjects aged 12 ± 4 years (48% males). Criteria proposed by the International Obesity Task Force (IOTF) and the Centers for Disease Control (CDC) were used to define obesity and overweight., Results: According to CDC criteria the prevalence of overweight and obesity was 11.2% and 6.5%, respectively. According to IOTF criteria, the fgures were 13.2 and 4%, respectively. The higher frequency of overweight and obesity was observed among children aged less than eight years., Conclusions: There is a high frequency of obesity and overweight in the studied sample.

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.