(Circulation. 1997;96:733-740.)
© 1997 American Heart Association, Inc.
Articles |
Lipoprotein Lipase Variants D9N and N291S Are Associated With Increased Plasma Triglyceride and Lower High-Density Lipoprotein Cholesterol Concentrations
Studies in the Fasting and Postprandial States: The European Atherosclerosis Research Studies
From the Department of Medicine and Cardiology A, Aarhus Amtssygehus University Hospital, Tage Hansensgade 2, DK-8000 C Aarhus, Denmark (C.G., O.F.); Division of Cardiovascular Genetics, University College London Medical School, London, UK (R.M.F., S.E.H., P.J.T.); and INSERM U258, Hôpital Broussais, Paris, France (V.N., J.B.).
Correspondence to Dr C. Gerdes, Department of Medicine and Cardiology A, Aarhus Amtssygehus University Hospital, Tage Hansensgade 2, DK-8000 C Aarhus, Denmark. E-mail c_gerdes{at}post4.tele.dk
Background Variations at the DNA level with moderate effects on biochemical variables may be important for the occurrence of disease at the population level, if they are common. Two mutations in the LPL gene, N9 and S291, are associated with variation in fasting plasma concentrations of HDL cholesterol (HDL-C) and triglycerides (TG). We investigated whether these mutants were more frequent in offspring of cases with premature coronary disease and analyzed the effects on fasting plasma lipids and postprandial TG.
Methods and Results Students with and without paternal history of myocardial infarction (cases and control subjects [controls]) were studied in the European Atherosclerosis Research Studies I and II (EARS-I and -II). Allelic frequencies for the N9 and S291 mutations did not differ between cases and control subjects. The N9 mutation was identified in 4.2% of all subjects in EARS-I, and carriers had higher fasting TG levels (P<.001) than noncarriers. In an oral fat tolerance test, there were no differences in postprandial TG between carriers and noncarriers of the N9 allele. The S291 mutation was identified in 3.1% of all subjects in EARS-I, and carriers had lower fasting HDL-C levels (P<.005) than noncarriers. There was a significant interaction between S291 genotype and body mass index on fasting TG levels (P<.01). In the cases, carriers of the S291 allele had higher TG levels 6 hours postprandially (P<.04) than did noncarriers.
Conclusions The two LPL mutations are common and may predispose to elevated TG and decreased HDL-C concentrations, even in young subjects. In the case of the S291 mutation, this effect appears to be mediated via delayed postprandial TG clearance. Moreover, even moderate obesity potentiates the TG-raising and HDL-lowering effects associated with the S291 allele.
Key Words: genetics • obesity • epidemiology • postprandial lipemia • EARS Group
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