Genotype-phenotype relationships in patients with type i hyperlipoproteinemia

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51 Scopus citations


Context 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. Design/Intervention Genetic screening for mutations in LPL, APOC2, GPIHBP1, LMF1, and APOA5. Setting Tertiary referral center. Patients Ten patients (7 female, 3 male) with chylomicronemia, serum triglyceride levels about 2000 mg/dL, and no secondary causes of hypertriglyceridemia. Main Outcome Measures 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.

Original languageEnglish (US)
Pages (from-to)287-295
Number of pages9
JournalJournal of Clinical Lipidology
Issue number3
StatePublished - 2014


  • Apolipoprotein A5
  • Familial chylomicronemia syndrome
  • Keywords
  • Lipoprotein lipase
  • Type 1 hyperlipoproteinemia

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Cardiology and Cardiovascular Medicine


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