ABSTRACT
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.
Subject(s)
Humans , Infant , Child, Preschool , Child , Adolescent , Proprotein Convertase 9/genetics , Hyperlipoproteinemia Type II/diagnosis , Hyperlipoproteinemia Type II/genetics , Hyperlipoproteinemia Type II/epidemiology , Chile , MutationABSTRACT
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.