title: Increased risk for endogenous hypertriglyceridaemia is associated with an apolipoprotein C3 haplotype specified by the SstI polymorphism.
abstract: BACKGROUND
  Hypertriglyceridaemia is a common metabolic disorder frequently found in patients with coronary heart disease. Numerous studies have revealed an association between the SstI polymorphism in the APOC3 gene and increased plasma apoC3 and triglyceride levels. In addition, two different variants within the promoter region have been recently suggested to be the mutations of the APOC3 gene leading to hypertriglyceridaemia.
  
  
  METHODS
  In the present study, we have applied haplotype analysis to investigate whether these promoter polymorphisms are involved in the lipid disorders of patients with distinct types of hypertriglyceridaemia: combined hyperlipidaemia (CHL), familial dysbetalipoproteinaemia (FD) and endogenous hypertriglyceridaemia (HTG).
  
  
  RESULTS
  The -482 and -455 polymorphisms were significantly more frequent in FD patients (P = 0. 017) and endogenous HTG patients (P < 0.0001) than in CHL patients and a control group. The SstI polymorphism was only significantly more frequent in HTG patients (P < 0.0001). However, we did not find differences in frequencies for these polymorphisms in the APOC3 gene between CHL patients and a control group. Haplotype analysis indicates that the SstI polymorphism arose on the allele containing both promoter polymorphisms.
  
  
  CONCLUSIONS
  The haplotype containing the SstI polymorphism is found five times more frequently among HTG patients (OR 5.28, 95% CI 1.65-16.90), which strongly suggests it is associated with an increased risk for severe hypertriglyceridaemia.
authors.affiliation: Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Hoffer
authors.forename: E J
authors.initials: EJ
authors.lastname: Sijbrands
authors.forename: F H
authors.initials: FH
authors.lastname: De Man
authors.forename: L M
authors.initials: LM
authors.lastname: Havekes
authors.forename: A H
authors.initials: AH
authors.lastname: Smelt
authors.forename: R R
authors.initials: RR
authors.lastname: Frants
mesh_terms: D000328:Adult; D000368:Aged; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000235:genetics*; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism*; D006239:Haplotypes; D006801:Humans; D015228:Hypertriglyceridemia / Q000209:etiology*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012306:Risk
chemical_list: D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; C024408:endodeoxyribonuclease SacI; D015252:Deoxyribonucleases, Type II Site-Specific