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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

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1437-4331
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Volume 57, Issue 7

Issues

Lipid profile and genetic status in a familial hypercholesterolemia pediatric population: exploring the LDL/HDL ratio

Maria Donata Di Taranto
  • Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Naples, Italy
  • CEINGE Biotecnologie Avanzate s.c. a r.l., Naples, Italy
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/ Renato de Falco
  • Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Naples, Italy
  • CEINGE Biotecnologie Avanzate s.c. a r.l., Naples, Italy
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/ Ornella Guardamagna
  • Dipartimento di Scienze della Sanità Pubblica e Pediatriche, Università degli Studi di Torino, Turin, Italy
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/ Giulia Massini
  • Dipartimento di Scienze della Sanità Pubblica e Pediatriche, Università degli Studi di Torino, Turin, Italy
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/ Carola Giacobbe
  • Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Naples, Italy
  • CEINGE Biotecnologie Avanzate s.c. a r.l., Naples, Italy
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/ Renata Auricchio
  • Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli Federico II, Naples, Italy
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/ Basilio Malamisura
  • Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli Federico II, Naples, Italy
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/ Michela Proto
  • Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli Federico II, Naples, Italy
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/ Daniela Palma
  • Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Naples, Italy
  • CEINGE Biotecnologie Avanzate s.c. a r.l., Naples, Italy
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/ Luigi Greco
  • Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli Federico II, Naples, Italy
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/ Giuliana Fortunato
  • Corresponding author
  • Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Naples, Italy
  • CEINGE Biotecnologie Avanzate s.c. a r.l., via Gaetano Salvatore 486, 80145 Naples, Italy, Phone: +39-081.746.4200
  • Email
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Published Online: 2019-02-02 | DOI: https://doi.org/10.1515/cclm-2018-1037

Abstract

Background

Familial hypercholesterolemia (FH) is a genetic disorder caused by mutations in genes involved in low-density lipoprotein (LDL) uptake (LDLR, APOB and PCSK9). Genetic diagnosis is particularly useful in asymptomatic children allowing for the detection of definite FH patients. Furthermore, defining their genetic status may be of considerable importance as the compound heterozygous status is much more severe than the heterozygous one. Our study aims at depicting the genetic background of an Italian pediatric population with FH focusing on the correlation between lipid profile and genetic status.

Methods

Out of 196 patients with clinically suspected FH (LDL-cholesterol [LDL-C] levels above 3.37 mmol/L, cholesterol level above 6.46 mmol/L in a first-degree relative or the presence of premature cardiovascular acute disease in a first/second-degree relative), we screened 164 index cases for mutations in the LDLR, APOB and PCSK9 genes.

Results

Patients with mutations (129/164) showed increased levels of LDL-C, 95th percentile-adjusted LDL-C and LDL/high-density lipoprotein (HDL) ratio and decreased levels of HDL-C, adjusted HDL-C. The association of the LDL/HDL ratio with the presence of mutations was assessed independently of age, (body mass index) BMI, parental hypercholesterolemia, premature coronary artery disease (CAD), triglycerides by multivariate logistic regression (odds ratio [OR]=1.701 [1.103–2.621], p=0.016). The LDL/HDL ratio gradually increased from patients without mutations to patients with missense mutations, null mutations and compound heterozygotes.

Conclusions

In conclusion, the LDL/HDL ratio proved to be a better parameter than LDL-C for discriminating patients with from patients without mutations across different genetic statuses.

This article offers supplementary material which is provided at the end of the article.

Keywords: compound heterozygotes; LDL/HDL ratio; missense mutation; molecular diagnosis; null mutation

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About the article

Corresponding author: Prof. Giuliana Fortunato, MD, PhD, Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, via S. Pansini 5, 80131 Naples, Italy


Received: 2018-09-21

Accepted: 2018-12-12

Published Online: 2019-02-02

Published in Print: 2019-06-26


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: This work was supported by MIUR funding under the project cod. PON03PE_00060_7, Italy.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 57, Issue 7, Pages 1102–1110, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2018-1037.

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