title: Severe hypertriglyceridaemia in Type II diabetes: involvement of apoC-III Sst-I polymorphism, LPL mutations and apo E3 deficiency.
abstract: OBJECTIVE
  Hypertriglyceridaemia is common in Type II (non-insulin-dependent) diabetes mellitus. Only subgroups of patient however have type V hyperlipidaemia. To investigate the coordination between genetic factors in the modulation of hypertriglyceridaemia in Type II diabetes, we studied three major modifier loci: apoC-III (both Sst-I and insulin-responsive element polymorphisms), apolipoprotein E genotypes and lipoprotein-lipase mutations.
  
  
  METHODS
  We studied apoCIII gene polymorphisms, apolipoprotein E genotypes and lipoprotein-lipase gene mutations in 176 patients with Type II (non-insulin-dependent) diabetes mellitus, either normolipaemic (group N, n = 116), mildly hypertriglyceridaemic (group T, n = 28) or with a history of severe hypertriglyceridaemia (triglyceride > 15 g/l) (group H, n = 32).
  
  
  RESULTS
  Mild hypertriglyceridaemia in Type II diabetes did not associate with any gene variants in this study. Severe hypertriglyceridaemia was, however, associated with the presence of the apoC-III S2 allele (50% of the patients in group H compared with 15.5 % in group N, p < 0.0001). Additionally this particular phenotype was associated with a low prevalence of the apo E3 allele (35.9% in group H vs 18.1 % in group N, p < 0.005) and a statistically significant over-representation of the E2E4 genotypes. Inactivating lipoprotein-lipase mutations were found in four patients (three heterozygotes, one homozygote), none was found in group N or T. Thus 68.7 % of group H patients (22/32) (vs 21.4 % in group T, p < 0.0005) were carriers of either S2 allele, lipoprotein-lipase mutants or E2E4 genotype with most lipoprotein-lipase mutants or E2E4 genotypes or both in the non-carriers for the S2 allele (6/7).
  
  
  CONCLUSIONS
  Our results strongly support the hypothesis that severe hyperlipaemia in Type II diabetes crucially depends on genetic factors which impair the clearance of triglyceride-rich lipoproteins.
authors: CNRS UMR5014 Laboratory, Lyon-I University, France.
authors: C
authors: C
authors: Marçais
authors: S
authors: S
authors: Bernard
authors: M
authors: M
authors: Merlin
authors: M
authors: M
authors: Ulhmann
authors: B
authors: B
authors: Mestre
authors: L
authors: L
authors: Rochet-Mingret
authors: A
authors: A
authors: Revol
authors: F
authors: F
authors: Berthezene
authors: P
authors: P
authors: Moulin
mesh_terms: D000328:Adult; D000368:Aged; D053305:Apolipoprotein C-III; D053318:Apolipoprotein E3; D001056:Apolipoproteins C / Q000235:genetics*; D001057:Apolipoproteins E / Q000172:deficiency*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015228:Hypertriglyceridemia / Q000150:complications / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D053305:Apolipoprotein C-III; D053318:Apolipoprotein E3; D001056:Apolipoproteins C; D001057:Apolipoproteins E; D008071:Lipoprotein Lipase