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Increased risk for endogenous hypertriglyceridaemia is associated with an apolipoprotein C3 haplotype specified by the Sst I polymorphism
Author(s) -
Hoffer,
Eric J.G. Sijbrands,
de Man,
Havekes,
Smelt,
Frants
Publication year - 1998
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.1998.00361.x
Subject(s) - haplotype , apolipoprotein b , medicine , biology , hypertriglyceridemia , allele , triglyceride , genetics , polymorphism (computer science) , endocrinology , cholesterol , gene
Background Hypertriglyceridaemia is a common metabolic disorder frequently found in patients with coronary heart disease. Numerous studies have revealed an association between the Sst I 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 Sst I 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 Sst I polymorphism arose on the allele containing both promoter polymorphisms. Conclusion The haplotype containing the Sst I 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.