title: Inherited apolipoprotein A-V deficiency in severe hypertriglyceridemia.
abstract: OBJECTIVE
  Mutations in LPL or APOC2 genes are recognized causes of inherited forms of severe hypertriglyceridemia. However, some hypertrigliceridemic patients do not have mutations in either of these genes. Because inactivation or hyperexpression of APOA5 gene, encoding apolipoprotein A-V (apoA-V), causes a marked increase or decrease of plasma triglycerides in mice, and because some common polymorphisms of this gene affect plasma triglycerides in humans, we have hypothesized that loss of function mutations in APOA5 gene might cause hypertriglyceridemia.
  
  
  RESULTS
  We sequenced APOA5 gene in 10 hypertriglyceridemic patients in whom mutations in LPL and APOC2 genes had been excluded. One of them was found to be homozygous for a mutation in APOA5 gene (c.433 C>T, Q145X), predicted to generate a truncated apoA-V devoid of key functional domains. The plasma of this patient was found to activate LPL in vitro less efficiently than control plasma, thus suggesting that apoA-V might be an activator of LPL. Ten carriers of Q145X mutation were found in the patient's family; 5 of them had mild hypertriglyceridemia.
  
  
  CONCLUSIONS
  As predicted from animal studies, apoA-V deficiency is associated with severe hypertriglyceridemia in humans. This observation suggests that apoA-V regulates the secretion and/or catabolism of triglyceride-rich lipoproteins. Mutations in APOA5 gene might be the cause of severe hypertriglyceridemia in subjects in whom mutations in LPL or APOC2 genes have been excluded. We detected a nonsense mutation in APOA5 gene (Q145X) in a boy with hyperchylomicronemia syndrome. This is the first observation of a complete apoA-V deficiency in humans.
authors.affiliation: Department of Biomedical Sciences, University of Modena and Reggio Emilia, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Priore Oliva
authors.forename: Livia
authors.initials: L
authors.lastname: Pisciotta
authors.forename: Giovanni
authors.initials: G
authors.lastname: Li Volti
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Sambataro
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cantafora
authors.forename: Antonella
authors.initials: A
authors.lastname: Bellocchio
authors.forename: Alberico
authors.initials: A
authors.lastname: Catapano
authors.forename: Patrizia
authors.initials: P
authors.lastname: Tarugi
authors.forename: Stefano
authors.initials: S
authors.lastname: Bertolini
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Calandra
mesh_terms: D019943:Amino Acid Substitution; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D001054:Apolipoproteins A; D002648:Child; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004789:Enzyme Activation; D005091:Exons / Q000235:genetics; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D006953:Hyperlipoproteinemia Type IV / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D007558:Italy; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D017354:Point Mutation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014416:Tunisia / Q000208:ethnology
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins; D001054:Apolipoproteins A; D015525:Fatty Acids, Omega-3; D008055:Lipids; D008074:Lipoproteins; D012333:RNA, Messenger; D008071:Lipoprotein Lipase