title: Genotype-phenotype relationships in patients with type I hyperlipoproteinemia.
abstract: BACKGROUND
  Type I hyperlipoproteinemia (T1HLP) is a rare, autosomal recessive disorder characterized by extreme hypertriglyceridemia that fails to respond to lipid-lowering agents, predisposing to frequent attacks of acute pancreatitis. Mutations in lipoprotein lipase (LPL), apolipoprotein CII (APOC2), lipase maturation factor 1 (LMF1), glycosyl-phosphatidylinositol anchored high-density lipoprotein-binding protein 1 (GPIHBP1), and apolipoprotein AV (APOA5) cause T1HLP, but we lack data on phenotypic variations among the different genetic subtypes.
  
  
  OBJECTIVE
  To study genotype-phenotype relationships among subtypes of T1HLP patients.
  
  
  METHODS
  Genetic screening for mutations in LPL, APOC2, GPIHBP1, LMF1, and APOA5.
  
  
  METHODS
  Tertiary referral center.
  
  
  METHODS
  Ten patients (7 female, 3 male) with chylomicronemia, serum triglyceride levels about 2000 mg/dL, and no secondary causes of hypertriglyceridemia.
  
  
  METHODS
  Genotyping and phenotypic features.
  
  
  RESULTS
  Four patients harbored homozygous or compound heterozygous mutations in LPL, 3 had homozygous mutations in GPIHBP1, and 1 had a heterozygous APOA5 mutation. We failed to fully identify the genetic etiology in 2 cases: 1 had a heterozygous LPL mutation only and another did not have any mutations. We identified 2 interesting phenotypic features: the patient with heterozygous APOA5 mutation normalized triglyceride levels with weight loss and fish oil therapy, and all 7 female patients were anemic.
  
  
  CONCLUSIONS
  Our data suggest the possibility of novel loci for T1HLP. We observed that heterozygous APOA5 mutation can cause T1HLP but such patients may unexpectedly respond to therapy, and females with T1HLP suffer from anemia. Further studies of larger cohorts may elucidate more phenotype-genotypes relationships among T1HLP subtypes.
authors.affiliation: Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, Center for Human Nutrition.
authors.forename: Neema
authors.initials: N
authors.lastname: Chokshi
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390.
authors.forename: Sarah D
authors.initials: SD
authors.lastname: Blumenschein
authors.affiliation: Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, Center for Human Nutrition.
authors.forename: Zahid
authors.initials: Z
authors.lastname: Ahmad
authors.affiliation: Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, Center for Human Nutrition. Electronic address: abhimanyu.garg@utsouthwestern.edu.
authors.forename: Abhimanyu
authors.initials: A
authors.lastname: Garg
mesh_terms: D000293:Adolescent; D000328:Adult; D000072040:Apolipoprotein A-V; D053304:Apolipoprotein C-II / Q000235:genetics; D001054:Apolipoproteins A / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004035:Diet Therapy; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000235:genetics* / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D018110:Receptors, Lipoprotein / Q000235:genetics*; D012737:Sex Factors; D055815:Young Adult
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D053304:Apolipoprotein C-II; D001054:Apolipoproteins A; C523701:GPIHBP1 protein, human; C546366:LMF1 protein, human; D008565:Membrane Proteins; D018110:Receptors, Lipoprotein; D008071:Lipoprotein Lipase
keywords: Apolipoprotein A5; Familial chylomicronemia syndrome; GPIHBP1; Lipoprotein lipase; Type 1 hyperlipoproteinemia