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.
authors: Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: Hajnalka
authors: H
authors: Lőrincz
authors: Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: Mariann
authors: M
authors: Harangi
authors: Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: Anna V
authors: AV
authors: Oláh
authors: Department of Pediatrics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: Gabriella P
authors: GP
authors: Szabó
authors: Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: Péter
authors: P
authors: Fülöp
authors: Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: Sándor
authors: S
authors: Somodi
authors: Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: György
authors: G
authors: Paragh
authors: Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: Ildikó
authors: I
authors: Seres
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D043303:Aryldialkylphosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D018384:Oxidative Stress; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000097:blood*; D010100:Oxygen / Q000737:chemistry; D019082:Smith-Lemli-Opitz Syndrome / Q000097:blood*
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D008076:Cholesterol, HDL; D008055:Lipids; D008075:Lipoproteins, HDL; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D010100:Oxygen