title: The type of LDLR gene mutation predicts cardiovascular risk in children with familial hypercholesterolemia.
abstract: OBJECTIVE
  To ascertain whether the molecular characterization of a defect in the low-density lipoprotein (LDL) receptor gene (LDLR) in children with heterozygous familial hypercholesterolemia (heFH) identifies subjects at greater risk of developing premature coronary artery disease (pCAD) later in life.
  
  
  METHODS
  We investigated 264 children with heFH from 201 families, along with 148 affected parents and 100 unaffected siblings. The lipid profile was assessed before any treatment was provided, and genotype analysis was performed to characterize LDLR defects. In a subgroup of children with heFH and controls, we measured aorta and carotid intima-media thickness (aIMT and cIMT). The prevalence of pCAD in parents and/or grandparents with heFH was recorded.
  
  
  RESULTS
  The children with heFH with a family history of pCAD had higher LDL cholesterol and apolipoprotein B levels and greater aIMT and cIMT than those with negative family history. Compared with carriers of LDLR-defective mutations, carriers of LDLR-negative mutations had a more severe phenotype, in terms of plasma lipid levels and IMT, and a higher prevalence of pCAD in first-degree relatives (36% vs 6.7%; P < .001).
  
  
  CONCLUSIONS
  The study of heFH in children, in which other risk factors for CAD play a minor role, allows early identification of those at increased risk for developing pCAD, who merit more stringent clinical control and early pharmacologic treatment.
authors.affiliation: Department of Pediatrics, University of Turin, Turin, Italy. ornella.guardamagna@unito.it
authors.forename: Ornella
authors.initials: O
authors.lastname: Guardamagna
authors.forename: Gabriella
authors.initials: G
authors.lastname: Restagno
authors.forename: Elio
authors.initials: E
authors.lastname: Rolfo
authors.forename: Cristina
authors.initials: C
authors.lastname: Pederiva
authors.forename: Scipione
authors.initials: S
authors.lastname: Martini
authors.forename: Francesca
authors.initials: F
authors.lastname: Abello
authors.forename: Viviana
authors.initials: V
authors.lastname: Baracco
authors.forename: Livia
authors.initials: L
authors.lastname: Pisciotta
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pino
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Calandra
authors.forename: Stefano
authors.initials: S
authors.lastname: Bertolini
mesh_terms: D000293:Adolescent; D000328:Adult; D001011:Aorta / Q000473:pathology; D001055:Apolipoproteins B / Q000097:blood; D002339:Carotid Arteries / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D007223:Infant; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012306:Risk; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology; D055815:Young Adult
chemical_list: D001055:Apolipoproteins B; D008078:Cholesterol, LDL; C514519:LDLR-related protein 1A, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D002784:Cholesterol