INCREASED RISK FOR ENDOGENOUS HYPERTRIGLYCERIDEMIA IS ASSOCIATED WITHAN APOLIPOPROTEIN C3 HAPLOTYPE SPECIFIED BY THE SSTI POLYMORPHISM

Background Hypertriglyceridaemia is a common metabolic disorder freque ntly found in patients with coronary heart disease. Numerous studies h ave 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 hypertrigly ceridaemia. Methods In the present study, we have applied haplotype an alysis to investigate whether these promoter polymorphisms are involve d in the lipid disorders of patients with distinct types of hypertrigl yceridaemia: combined hyperlipidaemia (CHL), familial dysbetalipoprote inaemia (FD) and endogenous hypertriglyceridaemia (HTG). Results The - 482 and -455 polymorphisms were significantly more frequent in FD pati ents (P=0.017) and endogenous HTG patients (P<0.0001) than in CHL pati ents and a control group. The SstI polymorphism was only significantly more frequent in HTG patients (P<0.0001). However, we did not find di fferences in frequencies for these polymorphisms in the APOC3 gene bet ween CHL patients and a control group. Haplotype analysis indicates th at the SstI polymorphism arose on the allele containing bath promoter polymorphisms. Conclusion The haplotype containing the SstI polymorphi sm 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 inc reased risk for severe hypertriglyceridaemia.