title: Effect of the amyloidogenic L75P apolipoprotein A-I variant on HDL subpopulations.
abstract: BACKGROUND
  Hereditary amyloidosis due to mutations of apolipoprotein A-I (apoA-I) is a rare disease characterized by the deposition of amyloid fibrils constituted by the N-terminal fragment of apoA-I in several organs. L75P is a variant of apoA-I associated with systemic amyloidosis predominantly involving the liver, kidneys, and testis, identified in a large number of unrelated subjects. Objective of the present paper was to evaluate the impact of the L75P apoA-I variant on HDL subpopulations and cholesterol esterification in carriers.
  
  
  RESULTS
  Plasma samples were collected from 30 carriers of the amyloidogenic L75P apoA-I (Carriers) and from 15 non affected relatives (Controls). Carriers displayed significantly reduced plasma levels of HDL-cholesterol, apoA-I, and apoA-II compared to Controls. Plasma levels of LpA-I, but not LpA-I:A-II, were significantly reduced in Carriers. HDL subclass distribution was not affected by the presence of the variant. The unesterified to total cholesterol ratio was higher, and cholesterol esterification rate and LCAT activity were lower in Carriers than in Controls.
  
  
  CONCLUSIONS
  The L75P apoA-I variant is associated with hypoalphalipoproteinemia, a selective reduction of LpA-I particles, and a partial defect in cholesterol esterification.
authors: Center Enrica Grossi Paoletti, Department of Pharmacological Sciences, Università degli Studi di Milano, Milano, Italy.
authors: Monica
authors: M
authors: Gomaraschi
authors: Laura
authors: L
authors: Obici
authors: Sara
authors: S
authors: Simonelli
authors: Gina
authors: G
authors: Gregorini
authors: Alessandro
authors: A
authors: Negrinelli
authors: Giampaolo
authors: G
authors: Merlini
authors: Guido
authors: G
authors: Franceschini
authors: Laura
authors: L
authors: Calabresi
mesh_terms: D028226:Amyloidosis, Familial / Q000235:genetics* / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000235:genetics*; D002784:Cholesterol / Q000378:metabolism; D018450:Disease Progression; D004951:Esterification / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation
chemical_list: D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D002784:Cholesterol