title: A silent mutation of Niemann-Pick C1-like 1 and apolipoprotein E4 modulate cholesterol absorption in primary hyperlipidemias.
abstract: OBJECTIVE
  To investigate the influence of the silent mutation c.816C > G (L272) of Niemann-Pick C1-like 1 (NPC1L1) and of apolipoprotein (APO) E alleles on cholesterol absorption markers, sitosterol and campesterol, in 87 patients with primary hyperlipidemias.
  
  
  METHODS
  In all subjects genotyped for silent polymorphism in NPC1L1 gene c.816C > G (L272L) and for APO E polymorphism, campesterol and sitosterol were measured by gas chromatography coupled to mass spectrometry.
  
  
  RESULTS
  Thirty-eight patients carrying the G allele of NPC1L1 showed significantly greater concentrations (log values) of campesterol (1.86 ± 0.3 vs 1.61 ± 0.3 10(2) μmol/mmol cholesterol, p < .001) and sitosterol (2.03 ± 0.2 vs 1.94 ± 0.2 10(2) μmol/mmol cholesterol, P = .05). Patients with at least one E4 allele showed values of sitosterol greater than those carrying E3E3 or E3E2 (2.05 ± 0.2 10(2) μmol/mmol cholesterol vs 1.95 ± 0.2 10(2) μmol/mmol cholesterol, P = .004). The presence of the G allele (β = .379, P < 0.001) and high-density lipoprotein cholesterol (β = .242, P = .019) was an independent predictor of campesterol values (R of the model = 0.473, P < .001). The E4 allele (β = .293, P = .005) and high-density lipoprotein cholesterol (β = .311, P = .003) were independent predictors of sitosterol values (R 0.416, P of the model <.001).
  
  
  CONCLUSIONS
  In patients with hyperlipidemias, G allele of NPC1L1 and APO E4 could account for some of the inter-individual variability in cholesterol absorption.
authors: Department of Clinical and Experimental Medicine, Internal Medicine, Angiology and Atherosclerosis, Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy. glupa@unipg.it
authors: Graziana
authors: G
authors: Lupattelli
authors: Livia
authors: L
authors: Pisciotta
authors: Stefano
authors: S
authors: De Vuono
authors: Donatella
authors: D
authors: Siepi
authors: Antonella
authors: A
authors: Bellocchio
authors: Francesco
authors: F
authors: Melis
authors: Stefano
authors: S
authors: Bertolini
authors: Matteo
authors: M
authors: Pirro
authors: Elmo
authors: E
authors: Mannarino
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D053327:Apolipoprotein E4 / Q000235:genetics* / Q000378:metabolism; D002784:Cholesterol / Q000031:analogs & derivatives / Q000032:analysis; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005838:Genotype; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D026901:Membrane Transport Proteins; D008875:Middle Aged; D010840:Phytosterols / Q000032:analysis; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D012855:Sitosterols / Q000032:analysis
chemical_list: D053327:Apolipoprotein E4; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; D010840:Phytosterols; D012855:Sitosterols; C021273:campesterol; C025473:gamma-sitosterol; D002784:Cholesterol