Severe hypertriglyceridaemia in Type II diabetes: involvement of apoC-III Sst-I polymorphism, LPL mutations and apo E3 deficiency

Aims/hypothesis. Hypertriglyceridaemia is common in Type II (non-insulin-de pendent) diabetes mellitus. Only subgroups of patient however have type V h yperlipidaemia. To investigate the coordination between genetic factors in the modulation of hypertriglyceridaemia in Type II diabetes, we studied thr ee major modifier loci: apoC-III (both Sst-I and insulin-responsive element polymorphisms), apolipoprotein E genotypes and lipoprotein-lipase mutation s. Methods. We studied apoCIII gene polymorphisms, apolipoprotein E genotypes and lipoprotein-lipase gene mutations in 176 patients with Type II (non-ins ulin-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 w ith any gene variants in this study. Severe hypertriglyceridaemia was, howe ver, associated with the presence of the apoC-III S2 allele (50% of the pat ients 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 E 3 allele (35.9% in group H vs 18.1% in group N,p < 0.005) and a statistical ly significant over-representation of the E2E4 genotypes. Inactivating lipo protein-lipase mutations were found in four patients (three heterozygotes, one homozygote), none was found in group N or T. Thus 68.7% of group K pati ents (22/32) (vs 21.4% in group T, p < 0.0005) were carriers of either S2 a llele, lipoprotein-lipase mutants or E2E4 genotype with most lipoprotein-li pase mutants or E2E4 genotypes or both in the non-carriers for the S2 allel e (6/7). Conclusion/interpretation. Our results strongly support the hypothesis that severe hyperlipaemia in Type II diabetes crucially depends on genetic fact ors which impair the clearance of triglyceride-rich Lipoproteins.