Altered lipid subfraction profile and impaired antioxidant defense of high-density lipoprotein in Smith-Lemli-Opitz syndrome

Hajnalka Lörincz, M. Harangi, Anna V. Oláh, Gabriella P. Szabó, Péter Fülöp, Sándor Somodi, G. Paragh, I. Seres

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background:Smith-Lemli-Opitz syndrome (SLOS) is a rare disease caused by biallelic mutation in the 7-dehydrocholesterol (7DHC) reductase gene. High oxidizability of 7DHC and the appearance of small-sized low-density lipoprotein (LDL) subfractions indicate increased endogenous oxidative stress that is counterbalanced by natural antioxidant defense mechanisms including the high-density lipoprotein (HDL)-associated paraoxonase-1 (PON1) enzyme. PON1 prevents lipoproteins from oxidative modifications; however, PON1 activity and the distribution of lipoprotein subfractions have not been studied in SLOS.Methods:7DHC levels and PON1 arylesterase activities were measured spectrophotometrically in 11 SLOS patients and 10 healthy children. Lipoprotein subfractions were detected by polyacrylamide gel electrophoresis.Results:Compared to controls, there was a shift towards the small-dense LDL subfraction and the large HDL subfraction in SLOS. PON1 arylesterase activity was significantly decreased in SLOS patients and correlated negatively with the proportion of small-dense LDL subfraction and the proportion of large HDL subfraction. Significant positive correlations were detected between PON1 arylesterase activity and the ratios of intermediate and small HDL subfractions.Conclusions:Decreased PON1 activity and the deleterious shift in the distribution of lipoprotein subfractions may contribute to the impaired antioxidant status observed in SLOS. Monitoring of serum PON1 arylesterase activity may be a complementary biomarker in SLOS.

Original languageEnglish
Pages (from-to)703-709
Number of pages7
JournalPediatric Research
Volume77
Issue number5
DOIs
Publication statusPublished - May 22 2015

Fingerprint

Smith-Lemli-Opitz Syndrome
Aryldialkylphosphatase
HDL Lipoproteins
Antioxidants
Lipids
Lipoproteins
LDL Lipoproteins
Rare Diseases
Polyacrylamide Gel Electrophoresis
Oxidative Stress
Biomarkers
Mutation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Altered lipid subfraction profile and impaired antioxidant defense of high-density lipoprotein in Smith-Lemli-Opitz syndrome. / Lörincz, Hajnalka; Harangi, M.; Oláh, Anna V.; Szabó, Gabriella P.; Fülöp, Péter; Somodi, Sándor; Paragh, G.; Seres, I.

In: Pediatric Research, Vol. 77, No. 5, 22.05.2015, p. 703-709.

Research output: Contribution to journalArticle

Lörincz, Hajnalka ; Harangi, M. ; Oláh, Anna V. ; Szabó, Gabriella P. ; Fülöp, Péter ; Somodi, Sándor ; Paragh, G. ; Seres, I. / Altered lipid subfraction profile and impaired antioxidant defense of high-density lipoprotein in Smith-Lemli-Opitz syndrome. In: Pediatric Research. 2015 ; Vol. 77, No. 5. pp. 703-709.
@article{0d8e4fcf07b94c558782f28037b3d550,
title = "Altered lipid subfraction profile and impaired antioxidant defense of high-density lipoprotein in Smith-Lemli-Opitz syndrome",
abstract = "Background:Smith-Lemli-Opitz syndrome (SLOS) is a rare disease caused by biallelic mutation in the 7-dehydrocholesterol (7DHC) reductase gene. High oxidizability of 7DHC and the appearance of small-sized low-density lipoprotein (LDL) subfractions indicate increased endogenous oxidative stress that is counterbalanced by natural antioxidant defense mechanisms including the high-density lipoprotein (HDL)-associated paraoxonase-1 (PON1) enzyme. PON1 prevents lipoproteins from oxidative modifications; however, PON1 activity and the distribution of lipoprotein subfractions have not been studied in SLOS.Methods:7DHC levels and PON1 arylesterase activities were measured spectrophotometrically in 11 SLOS patients and 10 healthy children. Lipoprotein subfractions were detected by polyacrylamide gel electrophoresis.Results:Compared to controls, there was a shift towards the small-dense LDL subfraction and the large HDL subfraction in SLOS. PON1 arylesterase activity was significantly decreased in SLOS patients and correlated negatively with the proportion of small-dense LDL subfraction and the proportion of large HDL subfraction. Significant positive correlations were detected between PON1 arylesterase activity and the ratios of intermediate and small HDL subfractions.Conclusions:Decreased PON1 activity and the deleterious shift in the distribution of lipoprotein subfractions may contribute to the impaired antioxidant status observed in SLOS. Monitoring of serum PON1 arylesterase activity may be a complementary biomarker in SLOS.",
author = "Hajnalka L{\"o}rincz and M. Harangi and Ol{\'a}h, {Anna V.} and Szab{\'o}, {Gabriella P.} and P{\'e}ter F{\"u}l{\"o}p and S{\'a}ndor Somodi and G. Paragh and I. Seres",
year = "2015",
month = "5",
day = "22",
doi = "10.1038/pr.2015.33",
language = "English",
volume = "77",
pages = "703--709",
journal = "Pediatric Research",
issn = "0031-3998",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Altered lipid subfraction profile and impaired antioxidant defense of high-density lipoprotein in Smith-Lemli-Opitz syndrome

AU - Lörincz, Hajnalka

AU - Harangi, M.

AU - Oláh, Anna V.

AU - Szabó, Gabriella P.

AU - Fülöp, Péter

AU - Somodi, Sándor

AU - Paragh, G.

AU - Seres, I.

PY - 2015/5/22

Y1 - 2015/5/22

N2 - Background:Smith-Lemli-Opitz syndrome (SLOS) is a rare disease caused by biallelic mutation in the 7-dehydrocholesterol (7DHC) reductase gene. High oxidizability of 7DHC and the appearance of small-sized low-density lipoprotein (LDL) subfractions indicate increased endogenous oxidative stress that is counterbalanced by natural antioxidant defense mechanisms including the high-density lipoprotein (HDL)-associated paraoxonase-1 (PON1) enzyme. PON1 prevents lipoproteins from oxidative modifications; however, PON1 activity and the distribution of lipoprotein subfractions have not been studied in SLOS.Methods:7DHC levels and PON1 arylesterase activities were measured spectrophotometrically in 11 SLOS patients and 10 healthy children. Lipoprotein subfractions were detected by polyacrylamide gel electrophoresis.Results:Compared to controls, there was a shift towards the small-dense LDL subfraction and the large HDL subfraction in SLOS. PON1 arylesterase activity was significantly decreased in SLOS patients and correlated negatively with the proportion of small-dense LDL subfraction and the proportion of large HDL subfraction. Significant positive correlations were detected between PON1 arylesterase activity and the ratios of intermediate and small HDL subfractions.Conclusions:Decreased PON1 activity and the deleterious shift in the distribution of lipoprotein subfractions may contribute to the impaired antioxidant status observed in SLOS. Monitoring of serum PON1 arylesterase activity may be a complementary biomarker in SLOS.

AB - Background:Smith-Lemli-Opitz syndrome (SLOS) is a rare disease caused by biallelic mutation in the 7-dehydrocholesterol (7DHC) reductase gene. High oxidizability of 7DHC and the appearance of small-sized low-density lipoprotein (LDL) subfractions indicate increased endogenous oxidative stress that is counterbalanced by natural antioxidant defense mechanisms including the high-density lipoprotein (HDL)-associated paraoxonase-1 (PON1) enzyme. PON1 prevents lipoproteins from oxidative modifications; however, PON1 activity and the distribution of lipoprotein subfractions have not been studied in SLOS.Methods:7DHC levels and PON1 arylesterase activities were measured spectrophotometrically in 11 SLOS patients and 10 healthy children. Lipoprotein subfractions were detected by polyacrylamide gel electrophoresis.Results:Compared to controls, there was a shift towards the small-dense LDL subfraction and the large HDL subfraction in SLOS. PON1 arylesterase activity was significantly decreased in SLOS patients and correlated negatively with the proportion of small-dense LDL subfraction and the proportion of large HDL subfraction. Significant positive correlations were detected between PON1 arylesterase activity and the ratios of intermediate and small HDL subfractions.Conclusions:Decreased PON1 activity and the deleterious shift in the distribution of lipoprotein subfractions may contribute to the impaired antioxidant status observed in SLOS. Monitoring of serum PON1 arylesterase activity may be a complementary biomarker in SLOS.

UR - http://www.scopus.com/inward/record.url?scp=84928252405&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84928252405&partnerID=8YFLogxK

U2 - 10.1038/pr.2015.33

DO - 10.1038/pr.2015.33

M3 - Article

C2 - 25668223

AN - SCOPUS:84928252405

VL - 77

SP - 703

EP - 709

JO - Pediatric Research

JF - Pediatric Research

SN - 0031-3998

IS - 5

ER -