title: Two novel rare variants of APOA5 gene found in subjects with severe hypertriglyceridemia.
abstract: BACKGROUND
  Common variants of APOA5 gene affect plasma triglyceride (TG) in the population and a number of rare variants APOA5 have been reported in individuals with hypertriglyceridemia (HTG).
  
  
  METHODS
  APOA5 was analysed in 98 HTG individuals (plasma TG >9 mmol/L) in whom no mutations in LPL and APOC2 had been found.
  
  
  RESULTS
  Two patients were found to be heterozygous for two novel APOA5 variants. The first variant (p.L253P) was identified in an obese male who consumed a diet rich in fat and simple sugars. He was also a carrier in trans of the common TG-raising p.S19W SNP (5*3 haplotype). The second variant (c.295-297 del GAG, p.E99 del) was found in a lean male with no life style or metabolic factors known to affect plasma TG. He was a carrier in trans of the TG-raising 5*2 haplotype and was homozygous for the rare c.1337T allele of a SNP of GCKR gene. No mutations in other genes affecting plasma TG (LMF1 and GPIHBP1) were found in these patients. These APOA5 variants, resulted to be deleterious in silico, were not found in 350 control subjects.
  
  
  CONCLUSIONS
  These novel APOA5 variants predispose to HTG in combination with other genetic or nutritional factors.
authors.affiliation: Department of Internal Medicine, University of Genoa, Viale Benedetto XV n. 6, 16132 Genoa, Italy. livia.pisciotta@unige.it
authors.forename: Livia
authors.initials: L
authors.lastname: Pisciotta
authors.forename: Raffaele
authors.initials: R
authors.lastname: Fresa
authors.forename: Antonella
authors.initials: A
authors.lastname: Bellocchio
authors.forename: Virgilia
authors.initials: V
authors.lastname: Guido
authors.forename: Claudio
authors.initials: C
authors.lastname: Priore Oliva
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Calandra
authors.forename: Stefano
authors.initials: S
authors.lastname: Bertolini
mesh_terms: D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics*; D006801:Humans; D015228:Hypertriglyceridemia / Q000235:genetics*; D008297:Male
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A