title: Presence and type of low density lipoprotein receptor (LDLR) mutation influences the lipid profile and response to lipid-lowering therapy in Brazilian patients with heterozygous familial hypercholesterolemia.
abstract: OBJECTIVE
  Familial hypercholesterolemia (FH) is an autosomal dominant disease caused mainly by LDLR mutations. This study assessed the influence of the presence and type of LDLR mutation on lipid profile and the response to lipid-lowering therapy in Brazilian patients with heterozygous FH.
  
  
  METHODS
  For 14 ± 3 months, 156 patients with heterozygous FH receiving atorvastatin were followed. Coding sequences of the LDLR gene were bidirectionally sequenced, and the type of LDLR mutations were classified according to their probable functional class.
  
  
  RESULTS
  The frequencies of the types of LDLR mutations were: null-mutation (n = 40, 25.6%), defective-mutation (n = 59, 37.8%), and without an identified mutation (n = 57, 36.6%). Baseline total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were higher in patients carrying a null mutation (9.9 ± 1.9 mmol/L, 7.9 ± 1.7 mmol/L), compared to those with a defective (8.9 ± 2.2 mmol/L, 7.0 ± 2.0 mmol/L), or no mutation (7.9 ± 1.9 mmol/L, 5.8 ± 1.9 mmol/L) (p < 0.001). After treatment, the proportion of patients attaining an LDL-C<3.4 mmol/L was significantly different among groups: null (22.5%), defective (27.1%), and without mutations (47.4%) (p = 0.02). The presence of LDLR mutations was independently associated with higher odds of not achieving the LDL-C cut-off (OR 9.07, 95% CI 1.41-58.16, p = 0.02).
  
  
  CONCLUSIONS
  Our findings indicate that the presence and type of LDLR mutations influence lipid profile and response to lipid-lowering therapy in Brazilian patients with heterozygous FH. Thus, more intensive care with pharmacological therapeutics should be performed in patients who have a molecular analysis indicating the presence of a LDLR mutation.
authors: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, SP, Brazil. Electronic address: pacaleb@usp.br.
authors: Paulo Caleb Junior Lima
authors: PC
authors: Santos
authors: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, SP, Brazil.
authors: Aline Cruz
authors: AC
authors: Morgan
authors: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, SP, Brazil.
authors: Cintia Elin
authors: CE
authors: Jannes
authors: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, SP, Brazil.
authors: Luciana
authors: L
authors: Turolla
authors: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, SP, Brazil.
authors: Jose Eduardo
authors: JE
authors: Krieger
authors: Lipid Clinic, Heart Institute (InCor), University of Sao Paulo Medical School, SP, Brazil.
authors: Raul D
authors: RD
authors: Santos
authors: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, SP, Brazil. Electronic address: alexandre.pereira@incor.usp.br.
authors: Alexandre Costa
authors: AC
authors: Pereira
mesh_terms: D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D001384:Azetidines / Q000627:therapeutic use; D001938:Brazil; D008078:Cholesterol, LDL / Q000097:blood; D000069438:Ezetimibe; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy* / Q000235:genetics*; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D001384:Azetidines; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D008055:Lipids; D011758:Pyrroles; D011973:Receptors, LDL; D000069059:Atorvastatin; D000069438:Ezetimibe
keywords: Familial hypercholesterolemia; LDLR gene; Lipid-lowering therapy; Type of mutation