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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

  • Paulo Caleb Junior Lima Santos
    Correspondence
    Corresponding authors. Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of Sao Paulo Medical School, Av. Dr. Enéas de Carvalho Aguiar, 44 Cerqueira César, São Paulo, SP CEP 05403-000, Brazil. Tel.: +55 11 2661 5929; fax: +55 11 2661 5022.
    Affiliations
    Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, SP, Brazil
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  • Aline Cruz Morgan
    Affiliations
    Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, SP, Brazil
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  • Cintia Elin Jannes
    Affiliations
    Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, SP, Brazil
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  • Luciana Turolla
    Affiliations
    Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, SP, Brazil
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  • Jose Eduardo Krieger
    Affiliations
    Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, SP, Brazil
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  • Raul D. Santos
    Affiliations
    Lipid Clinic, Heart Institute (InCor), University of Sao Paulo Medical School, SP, Brazil
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  • Alexandre Costa Pereira
    Correspondence
    Corresponding authors. Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of Sao Paulo Medical School, Av. Dr. Enéas de Carvalho Aguiar, 44 Cerqueira César, São Paulo, SP CEP 05403-000, Brazil. Tel.: +55 11 2661 5929; fax: +55 11 2661 5022.
    Affiliations
    Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, SP, Brazil
    Search for articles by this author

      Highlights

      • 156 patients with FH receiving atorvastatin were followed for 12 months.
      • The presence and type of LDLR mutations influence response to lipid-lowering therapy.
      • More aggressive treatment should be practiced in FH patients with an LDLR mutation.

      Abstract

      Objectives

      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.

      Keywords

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